{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T02:18:14Z","timestamp":1791944294921,"version":"4.3.4"},"reference-count":202,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,10,3]],"date-time":"2020-10-03T00:00:00Z","timestamp":1601683200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Cancer Research Institute CLIP Award","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]},{"name":"Case Comprehensive Cancer Center American Cancer Society Pilot Grant","award":["IRG-91-022-19"],"award-info":[{"award-number":["IRG-91-022-19"]}]},{"name":"Case Comprehensive Cancer Center American Cancer Society Pilot Grants","award":["IRG-16-186-21"],"award-info":[{"award-number":["IRG-16-186-21"]}]},{"name":"Cleveland Digestive Diseases Research Core Center Pilot Grant","award":["1P30DK097948"],"award-info":[{"award-number":["1P30DK097948"]}]},{"name":"Immunology T32 Training Program","award":["AI089474"],"award-info":[{"award-number":["AI089474"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Molecular chaperones are a set of conserved proteins that have evolved to assist the folding of many newly synthesized proteins by preventing their misfolding under conditions such as elevated temperatures, hypoxia, acidosis and nutrient deprivation. Molecular chaperones belong to the heat shock protein (HSP) family. They have been identified as important participants in immune functions including antigen presentation, immunostimulation and immunomodulation, and play crucial roles in metabolic rewiring and epigenetic circuits. Growing evidence has accumulated to indicate that metabolic pathways and their metabolites influence the function of immune cells and can alter transcriptional activity through epigenetic modification of (de)methylation and (de)acetylation. However, whether molecular chaperones can regulate metabolic programs to influence immune activity is still largely unclear. In this review, we discuss the available data on the biological function of molecular chaperones to immune responses during inflammation, with a specific focus on the interplay between molecular chaperones and metabolic pathways that drive immune cell fate and function.<\/jats:p>","DOI":"10.3390\/metabo10100394","type":"journal-article","created":{"date-parts":[[2020,10,5]],"date-time":"2020-10-05T08:35:57Z","timestamp":1601886957000},"page":"394","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Molecular Chaperones: Molecular Assembly Line Brings Metabolism and Immunity in Shape"],"prefix":"10.3390","volume":"10","author":[{"given":"Haoxin","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydia N.","family":"Raines","sequence":"additional","affiliation":[{"name":"Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6557-3737","authenticated-orcid":false,"given":"Stanley Ching-Cheng","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA"},{"name":"Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1146\/annurev-biochem-060208-092442","article-title":"Molecular chaperone functions in protein folding and proteostasis","volume":"82","author":"Kim","year":"2013","journal-title":"Annu. Rev. Biochem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1038\/nature10317","article-title":"Molecular chaperones in protein folding and proteostasis","volume":"475","author":"Hartl","year":"2011","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1189\/jlb.1209779","article-title":"Molecular chaperones and protein-folding catalysts as intercellular signaling regulators in immunity and inflammation","volume":"88","author":"Henderson","year":"2010","journal-title":"J. Leukoc. Biol."},{"key":"ref_4","first-page":"169","article-title":"Heat shock proteins as ligands of toll-like receptors","volume":"270","author":"Vabulas","year":"2002","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Zininga, T., Ramatsui, L., and Shonhai, A. (2018). Heat Shock Proteins as Immunomodulants. Molecules, 23.","DOI":"10.3390\/molecules23112846"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1146\/annurev-immunol-032713-120236","article-title":"Metabolic regulation of immune responses","volume":"32","author":"Ganeshan","year":"2014","journal-title":"Annu. Rev. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1084\/jem.20151570","article-title":"Immunometabolism governs dendritic cell and macrophage function","volume":"213","author":"Pearce","year":"2016","journal-title":"J. Exp. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.3389\/fimmu.2019.02099","article-title":"Metabolic Insight of Neutrophils in Health and Disease","volume":"10","author":"Kumar","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1074\/jbc.R115.693903","article-title":"Immunometabolism: Cellular Metabolism Turns Immune Regulator","volume":"291","author":"Loftus","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1016\/j.molcel.2020.04.002","article-title":"Cytokine-like Roles for Metabolites in Immunity","volume":"78","year":"2020","journal-title":"Mol. Cell."},{"key":"ref_11","first-page":"13207","article-title":"Circles of Life: Linking metabolic and epigenetic cycles to immunity","volume":"16","author":"Lio","year":"2020","journal-title":"Immunology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.semcdb.2018.05.015","article-title":"It\u2019s not magic-Hsp90 and its effects on genetic and epigenetic variation","volume":"88","author":"Zabinsky","year":"2019","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/bs.acr.2015.09.003","article-title":"Hsp90 as a \"Chaperone\" of the Epigenome: Insights and Opportunities for Cancer Therapy","volume":"129","author":"Isaacs","year":"2016","journal-title":"Adv. Cancer Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1016\/j.molcel.2016.05.029","article-title":"Interplay between Metabolism and Epigenetics: A Nuclear Adaptation to Environmental Changes","volume":"62","author":"Etchegaray","year":"2016","journal-title":"Mol. Cell"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1038\/ncb3629","article-title":"The impact of cellular metabolism on chromatin dynamics and epigenetics","volume":"19","author":"Reid","year":"2017","journal-title":"Nat. Cell Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1007\/BF02172188","article-title":"A new puffing pattern induced by temperature shock and DNP in drosophila","volume":"18","author":"Ritossa","year":"1962","journal-title":"Experientia"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/0022-2836(74)90447-1","article-title":"Protein synthesis in salivary glands of Drosophila melanogaster: Relation to chromosome puffs","volume":"84","author":"Mitchell","year":"1974","journal-title":"J. Mol. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1007\/BF00321231","article-title":"Patterns of puffing activity in the salivary gland chromosomes of Drosophila","volume":"31","author":"Ashburner","year":"1970","journal-title":"Chromosoma"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1126\/science.3083508","article-title":"Abnormal proteins serve as eukaryotic stress signals and trigger the activation of heat shock genes","volume":"232","author":"Ananthan","year":"1986","journal-title":"Science"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/333330a0","article-title":"Homologous plant and bacterial proteins chaperone oligomeric protein assembly","volume":"333","author":"Hemmingsen","year":"1988","journal-title":"Nature"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/s12192-008-0068-7","article-title":"Guidelines for the nomenclature of the human heat shock proteins","volume":"14","author":"Kampinga","year":"2009","journal-title":"Cell Stress Chaperones"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Vabulas, R.M., Raychaudhuri, S., Hayer-Hartl, M., and Hartl, F.U. (2010). Protein folding in the cytoplasm and the heat shock response. Cold Spring Harb Perspect. Biol., 2.","DOI":"10.1101\/cshperspect.a004390"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/0092-8674(91)90452-5","article-title":"Heat shock factor and the heat shock response","volume":"65","author":"Sorger","year":"1991","journal-title":"Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4112","DOI":"10.1111\/j.1742-4658.2010.07827.x","article-title":"The heat shock factor family and adaptation to proteotoxic stress","volume":"277","author":"Fujimoto","year":"2010","journal-title":"FEBS J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/S0092-8674(00)81588-3","article-title":"Repression of Heat Shock Transcription Factor HSF1 Activation by HSP90 (HSP90 Complex) that Forms a Stress-Sensitive Complex with HSF1","volume":"94","author":"Zou","year":"1998","journal-title":"Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"31332","DOI":"10.1074\/jbc.M103217200","article-title":"Endocytosed HSP60s use toll-like receptor 2 (TLR2) and TLR4 to activate the toll\/interleukin-1 receptor signaling pathway in innate immune cells","volume":"276","author":"Vabulas","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"15028","DOI":"10.1074\/jbc.M200497200","article-title":"Novel signal transduction pathway utilized by extracellular HSP70: Role of toll-like receptor (TLR) 2 and TLR4","volume":"277","author":"Asea","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1479-0556-6-3","article-title":"A DNA vaccine against tuberculosis based on the 65 kDa heat-shock protein differentially activates human macrophages and dendritic cells","volume":"6","author":"Franco","year":"2008","journal-title":"Genet. Vaccines Ther."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Wu, M., Zhao, H., Li, M., Yue, Y., Xiong, S., and Xu, W. (2017). Intranasal Vaccination with Mannosylated Chitosan Formulated DNA Vaccine Enables Robust IgA and Cellular Response Induction in the Lungs of Mice and Improves Protection against Pulmonary Mycobacterial Challenge. Front. Cell. Infect. Microbiol., 7.","DOI":"10.3389\/fcimb.2017.00445"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1586\/14760584.7.3.383","article-title":"Heat-shock protein-based vaccines for cancer and infectious disease","volume":"7","author":"Binder","year":"2008","journal-title":"Expert Rev. Vaccines"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/77835","article-title":"CD91: A receptor for heat shock protein gp96","volume":"1","author":"Binder","year":"2000","journal-title":"Nat. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1016\/j.cell.2017.04.004","article-title":"Metabolic Instruction of Immunity","volume":"169","author":"Buck","year":"2017","journal-title":"Cell"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Zhao, H., Raines, L.N., and Huang, S.C.-C. (2020). Carbohydrate and Amino Acid Metabolism as Hallmarks for Innate Immune Cell Activation and Function. Cells, 9.","DOI":"10.3390\/cells9030562"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/nature22367","article-title":"Chromatin states define tumour-specific T cell dysfunction and reprogramming","volume":"545","author":"Philip","year":"2017","journal-title":"Nature"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1038\/ni.1920","article-title":"The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection","volume":"11","author":"Satoh","year":"2010","journal-title":"Nat. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1038\/s41467-019-13668-3","article-title":"Mitochondrial TCA cycle metabolites control physiology and disease","volume":"11","author":"Chandel","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Franco, F., Jaccard, A., Romero, P., Yu, Y.-R., and Ho, P.-C. (2020). Metabolic and epigenetic regulation of T-cell exhaustion. Nat. Metab., 1\u201312.","DOI":"10.1038\/s42255-020-00280-9"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.2217\/epi.15.71","article-title":"Metabolic-epigenetic crosstalk in macrophage activation","volume":"7","author":"Baardman","year":"2015","journal-title":"Epigenomics"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1016\/j.immuni.2017.04.016","article-title":"Metabolic and Epigenetic Coordination of T Cell and Macrophage Immunity","volume":"46","author":"Phan","year":"2017","journal-title":"Immunity"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Hoter, A., El-Sabban, M.E., and Naim, H.Y. (2018). The HSP90 Family: Structure, Regulation, Function, and Implications in Health and Disease. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19092560"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2439","DOI":"10.1042\/BCJ20160005","article-title":"Mechanisms of Hsp90 regulation","volume":"473","author":"Prodromou","year":"2016","journal-title":"Biochem. J."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Jackson, S. (2013). Hsp90: Structure and Function. Molecular Chaperones, Springer.","DOI":"10.1007\/128_2012_356"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/nrm.2017.20","article-title":"The HSP90 chaperone machinery","volume":"18","author":"Schopf","year":"2017","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1177\/153537020322800201","article-title":"Regulation of Signaling Protein Function and Trafficking by the hsp90\/hsp70-Based Chaperone Machinery","volume":"228","author":"Pratt","year":"2003","journal-title":"Exp. Biol. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1189\/jlb.0109005","article-title":"Heat shock proteins and immune system","volume":"85","author":"Tsan","year":"2009","journal-title":"J. Leukoc. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1093\/intimm\/dxq475","article-title":"Extracellular heat shock protein 90 plays a role in translocating chaperoned antigen from endosome to proteasome for generating antigenic peptide to be cross-presented by dendritic cells","volume":"23","author":"Oura","year":"2011","journal-title":"Int. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"16363","DOI":"10.1073\/pnas.1108372108","article-title":"Heat shock protein 90 (HSP90) contributes to cytosolic translocation of extracellular antigen for cross-presentation by dendritic cells","volume":"108","author":"Imai","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1093\/intimm\/dxg104","article-title":"Fever-like temperature induces maturation of dendritic cells through induction of hsp90","volume":"15","author":"Basu","year":"2003","journal-title":"Int. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/bs.acr.2015.10.001","article-title":"HSP90 and Immune Modulation in Cancer","volume":"129","author":"Graner","year":"2016","journal-title":"Adv. Cancer Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.2174\/156652412803306666","article-title":"Dual role of heat shock proteins (HSPs) in anti-tumor immunity","volume":"12","author":"Multhoff","year":"2012","journal-title":"Curr. Mol. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.tcb.2006.12.002","article-title":"Molecular chaperones and protein kinase quality control","volume":"17","author":"Caplan","year":"2007","journal-title":"Trends Cell Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"106","DOI":"10.4103\/2319-4170.113230","article-title":"Structure, function and regulation of the hsp90 machinery","volume":"36","author":"Li","year":"2013","journal-title":"Biomed. J."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1002\/hep.24802","article-title":"Inhibition of heat shock protein (molecular weight 90 kDa) attenuates proinflammatory cytokines and prevents lipopolysaccharide-induced liver injury in mice","volume":"55","author":"Ambade","year":"2012","journal-title":"Hepatology"},{"key":"ref_54","first-page":"51","article-title":"Interplay between HSP90 and Nrf2 pathways in diabetes-associated atherosclerosis","volume":"29","author":"Lazaro","year":"2017","journal-title":"Clin. Investig. Arter."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2020","DOI":"10.1038\/s41419-020-2460-x","article-title":"Carnosol inhibits inflammasome activation by directly targeting HSP90 to treat inflammasome-mediated diseases","volume":"11","author":"Shi","year":"2020","journal-title":"Cell Death. Dis."},{"key":"ref_56","first-page":"14338","article-title":"Inhibition of HSP90 and activation of HSF1 diminishes macrophage NLRP3 inflammasome activity in alcoholic liver injury","volume":"13","author":"Choudhury","year":"2020","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1084\/jem.20111117","article-title":"Inhibiting the HSP90 chaperone destabilizes macrophage migration inhibitory factor and thereby inhibits breast tumor progression","volume":"209","author":"Schulz","year":"2012","journal-title":"J. Exp. Med."},{"key":"ref_58","first-page":"14019","article-title":"HSP90A inhibition promotes anti-tumor immunity by reversing multi-modal resistance and stem-like property of immune-refractory tumors","volume":"11","author":"Song","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2139","DOI":"10.1038\/ncomms3139","article-title":"Landscape of the mitochondrial Hsp90 metabolome in tumours","volume":"4","author":"Chae","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/j.cellsig.2011.12.001","article-title":"Hsp90 interacts with AMPK and mediates acetyl-CoA carboxylase phosphorylation","volume":"24","author":"Zhang","year":"2012","journal-title":"Cell. Signal."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"017","DOI":"10.1186\/s12943-017-0748-y","article-title":"HSP90 promotes cell glycolysis, proliferation and inhibits apoptosis by regulating PKM2 abundance via Thr-328 phosphorylation in hepatocellular carcinoma","volume":"16","author":"Xu","year":"2017","journal-title":"Mol. Cancer"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3211","DOI":"10.1158\/1538-7445.AM2012-3211","article-title":"Abstract 3211: Inhibition of Hsp90 impairs expression of VDAC in plasma and mitochondrial membrane influencing cancer cell metabolism","volume":"72","author":"Mycielska","year":"2012","journal-title":"Cancer Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1186\/1423-0127-17-30","article-title":"Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin inhibits the proliferation of ARPE-19 cells","volume":"17","author":"Yao","year":"2010","journal-title":"J. Biomed. Sci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.cell.2012.03.003","article-title":"MYC on the path to cancer","volume":"149","author":"Dang","year":"2012","journal-title":"Cell"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.immuni.2011.09.021","article-title":"The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation","volume":"35","author":"Wang","year":"2011","journal-title":"Immunity"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1038\/onc.2012.144","article-title":"The ubiquitin ligase CHIP regulates c-Myc stability and transcriptional activity","volume":"32","author":"Paul","year":"2013","journal-title":"Oncogene"},{"key":"ref_67","first-page":"105","article-title":"Hsp90 inhibition increases p53 expression and destabilizes MYCN and MYC in neuroblastoma","volume":"38","author":"Regan","year":"2011","journal-title":"Int J. Oncol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/S0014-5793(99)01359-9","article-title":"Hypoxia-induced activation of HIF-1: Role of HIF-1alpha-Hsp90 interaction","volume":"460","author":"Minet","year":"1999","journal-title":"FEBS Lett."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.18632\/oncotarget.1734","article-title":"Targeting aerobic glycolysis and HIF-1alpha expression enhance imiquimod-induced apoptosis in cancer cells","volume":"5","author":"Huang","year":"2014","journal-title":"Oncotarget"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3699","DOI":"10.1172\/JCI84431","article-title":"HIF1\u03b1 and metabolic reprogramming in inflammation","volume":"126","author":"Corcoran","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s12950-017-0161-8","article-title":"HIF1\u03b1-Induced Glycolysis Metabolism Is Essential to the Activation of Inflammatory Macrophages","volume":"9029327","author":"Wang","year":"2017","journal-title":"Mediat. Inflamm."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"4697","DOI":"10.4049\/jimmunol.180.7.4697","article-title":"Hypoxia and Hypoxia-Inducible Factor-1\u03b1 Modulate Lipopolysaccharide-Induced Dendritic Cell Activation and Function","volume":"180","author":"Jantsch","year":"2008","journal-title":"J. Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1007\/s10620-010-1294-2","article-title":"Targeting PI3K\/Akt\/HSP90 signaling sensitizes gastric cancer cells to deoxycholate-induced apoptosis","volume":"56","author":"Redlak","year":"2011","journal-title":"Dig. Dis. Sci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/S1074-7613(02)00323-0","article-title":"The CD28 Signaling Pathway Regulates Glucose Metabolism","volume":"16","author":"Frauwirth","year":"2002","journal-title":"Immunity"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1016\/j.cell.2011.03.054","article-title":"Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxia-inducible factor 1","volume":"145","author":"Luo","year":"2011","journal-title":"Cell"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.cmet.2014.12.005","article-title":"Pyruvate kinase M2 regulates Hif-1\u03b1 activity and IL-1\u03b2 induction and is a critical determinant of the warburg effect in LPS-activated macrophages","volume":"21","author":"Curtis","year":"2015","journal-title":"Cell Metab."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.cmet.2019.10.015","article-title":"Pharmacological Activation of Pyruvate Kinase M2 Inhibits CD4(+) T Cell Pathogenicity and Suppresses Autoimmunity","volume":"31","author":"Angiari","year":"2020","journal-title":"Cell Metab."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"43","DOI":"10.4137\/GEG.S32160","article-title":"Epigenetics and Cellular Metabolism","volume":"8","author":"Xu","year":"2016","journal-title":"Genet. Epigenet."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/j.cell.2012.07.018","article-title":"PKM2 phosphorylates histone H3 and promotes gene transcription and tumorigenesis","volume":"150","author":"Yang","year":"2012","journal-title":"Cell"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1016\/j.molcel.2012.01.001","article-title":"Pyruvate kinase M2 regulates gene transcription by acting as a protein kinase","volume":"45","author":"Gao","year":"2012","journal-title":"Mol. Cell"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1038\/s41586-019-1678-1","article-title":"Metabolic regulation of gene expression by histone lactylation","volume":"574","author":"Zhang","year":"2019","journal-title":"Nature"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.4049\/jimmunol.0900592","article-title":"Gene regulation and chromatin remodeling by IL-12 and type I IFN in programming for CD8 T cell effector function and memory","volume":"183","author":"Agarwal","year":"2009","journal-title":"J. Immunol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"8102","DOI":"10.4049\/jimmunol.180.12.8102","article-title":"Histone acetylation facilitates rapid and robust memory CD8 T cell response through differential expression of effector molecules (eomesodermin and its targets: Perforin and granzyme B)","volume":"180","author":"Araki","year":"2008","journal-title":"J. Immunol."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Masgras, I., Sanchez-Martin, C., Colombo, G., and Rasola, A. (2017). The Chaperone TRAP1 As a Modulator of the Mitochondrial Adaptations in Cancer Cells. Front. Oncol., 7.","DOI":"10.3389\/fonc.2017.00058"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Matassa, D.S., Agliarulo, I., Avolio, R., Landriscina, M., and Esposito, F. (2018). TRAP1 Regulation of Cancer Metabolism: Dual Role as Oncogene or Tumor Suppressor. Genes, 9.","DOI":"10.3390\/genes9040195"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1007\/s12192-016-0687-3","article-title":"Past, present, and emerging roles of mitochondrial heat shock protein TRAP1 in the metabolism and regulation of cancer stem cells","volume":"21","author":"Im","year":"2016","journal-title":"Cell Stress Chaperones"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Joshi, A., Dai, L., Liu, Y., Lee, J., Ghahhari, N.M., Segala, G., Beebe, K., Jenkins, L.M., Lyons, G.C., and Bernasconi, L. (2020). The mitochondrial HSP90 paralog TRAP1 forms an OXPHOS-regulated tetramer and is involved in mitochondrial metabolic homeostasis. BMC Biol., 18.","DOI":"10.1186\/s12915-020-0740-7"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1016\/j.cmet.2013.04.019","article-title":"The Mitochondrial Chaperone TRAP1 Promotes Neoplastic Growth by Inhibiting Succinate Dehydrogenase","volume":"17","author":"Sciacovelli","year":"2013","journal-title":"Cell Metab."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"E1604","DOI":"10.1073\/pnas.1220659110","article-title":"Molecular chaperone TRAP1 regulates a metabolic switch between mitochondrial respiration and aerobic glycolysis","volume":"110","author":"Yoshida","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"3702","DOI":"10.1016\/j.febslet.2007.05.039","article-title":"The heat shock protein 70 family: Highly homologous proteins with overlapping and distinct functions","volume":"581","author":"Daugaard","year":"2007","journal-title":"FEBS Lett."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1038\/s41580-019-0133-3","article-title":"The Hsp70 chaperone network","volume":"20","author":"Rosenzweig","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_92","unstructured":"Fern\u00e1ndez-Fern\u00e1ndez, M.R., and Valpuesta, J.M. (1000). Hsp70 chaperone: A master player in protein homeostasis. F1000Research, 19."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1002\/jcp.1041380206","article-title":"Selective release from cultured mammalian cells of heat-shock (stress) proteins that resemble glia-axon transfer proteins","volume":"138","author":"Hightower","year":"1989","journal-title":"J. Cell Physiol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"15107","DOI":"10.1074\/jbc.M111204200","article-title":"HSP70 as endogenous stimulus of the Toll\/interleukin-1 receptor signal pathway","volume":"277","author":"Vabulas","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.jss.2006.06.003","article-title":"HSP70 enhances macrophage phagocytosis by interaction with lipid raft-associated TLR-7 and upregulating p38 MAPK and PI3K pathways","volume":"136","author":"Wang","year":"2006","journal-title":"J. Surg Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"455","DOI":"10.3109\/02656736.2013.798037","article-title":"Extracellular Hsp70 inhibits pro-inflammatory cytokine production by IL-10 driven down-regulation of C\/EBPbeta and C\/EBPdelta","volume":"29","author":"Borges","year":"2013","journal-title":"Int. J. Hyperth."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"12387","DOI":"10.1074\/jbc.M111.307579","article-title":"Inducible heat shock protein 70 reduces T cell responses and stimulatory capacity of monocyte-derived dendritic cells","volume":"287","author":"Stocki","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1111\/j.1365-2249.2004.02351.x","article-title":"Mycobacterial heat shock protein 70 induces interleukin-10 production: Immunomodulation of synovial cell cytokine profile and dendritic cell maturation","volume":"135","author":"Detanico","year":"2004","journal-title":"Clin. Exp. Immunol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1975","DOI":"10.4049\/jimmunol.1303468","article-title":"Moderate alcohol induces stress proteins HSF1 and hsp70 and inhibits proinflammatory cytokines resulting in endotoxin tolerance","volume":"193","author":"Muralidharan","year":"2014","journal-title":"J. Immunol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.radonc.2011.05.056","article-title":"Radiation combined with hyperthermia induces HSP70-dependent maturation of dendritic cells and release of pro-inflammatory cytokines by dendritic cells and macrophages","volume":"101","author":"Schildkopf","year":"2011","journal-title":"Radiother. Oncol. J. Eur. Soc. Ther. Radiol. Oncol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1089\/vim.2010.0052","article-title":"Dengue virus infection activates cellular chaperone Hsp70 in THP-1 cells: Downregulation of Hsp70 by siRNA revealed decreased viral replication","volume":"23","author":"Padwad","year":"2010","journal-title":"Viral Immunol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"3145","DOI":"10.1016\/j.febslet.2006.04.066","article-title":"Hsp70 inhibits lipopolysaccharide-induced NF-kappaB activation by interacting with TRAF6 and inhibiting its ubiquitination","volume":"580","author":"Chen","year":"2006","journal-title":"FEBS Lett."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1006\/cyto.2001.0959","article-title":"Over-expression of hsp-70 inhibits bacterial lipopolysaccharide-induced production of cytokines in human monocyte-derived macrophages","volume":"16","author":"Ding","year":"2001","journal-title":"Cytokine"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1016\/j.celrep.2020.01.005","article-title":"Distinct Transcriptional Responses across Tissue-Resident Macrophages to Short-Term and Long-Term Metabolic Challenge","volume":"30","author":"Brykczynska","year":"2020","journal-title":"Cell Rep."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1073\/pnas.0705799105","article-title":"HSP72 protects against obesity-induced insulin resistance","volume":"105","author":"Chung","year":"2008","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1016\/j.molmet.2014.08.003","article-title":"Chaperoning to the metabolic party: The emerging therapeutic role of heat-shock proteins in obesity and type 2 diabetes","volume":"3","author":"Henstridge","year":"2014","journal-title":"Mol. Metab."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1055\/s-0028-1128142","article-title":"Improvement of insulin sensitivity by a novel drug, BGP-15, in insulin-resistant patients: A proof of concept randomized double-blind clinical trial","volume":"41","author":"Kulcsar","year":"2009","journal-title":"Horm. Metab. Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1038\/74697","article-title":"HSP70 stimulates cytokine production through a CD14-dependant pathway, demonstrating its dual role as a chaperone and cytokine","volume":"6","author":"Asea","year":"2000","journal-title":"Nat. Med."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Anand, P.K., Anand, E., Bleck, C.K., Anes, E., and Griffiths, G. (2010). Exosomal Hsp70 induces a pro-inflammatory response to foreign particles including mycobacteria. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0010136"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"5424","DOI":"10.4049\/jimmunol.169.10.5424","article-title":"Tumor-Derived Heat Shock Protein 70 Peptide Complexes Are Cross-Presented by Human Dendritic Cells","volume":"169","author":"Noessner","year":"2002","journal-title":"J. Immunol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1038\/nm962","article-title":"Hsp70 promotes antigen-presenting cell function and converts T-cell tolerance to autoimmunity in vivo","volume":"9","author":"Millar","year":"2003","journal-title":"Nat. Med."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"2373","DOI":"10.1158\/0008-5472.CAN-06-3796","article-title":"High levels of heat shock protein Hsp72 in cancer cells suppress default senescence pathways","volume":"67","author":"Yaglom","year":"2007","journal-title":"Cancer Res."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1379\/1466-1268(2001)006<0337:AMHPSN>2.0.CO;2","article-title":"A 14-mer Hsp70 peptide stimulates natural killer (NK) cell activity","volume":"6","author":"Multhoff","year":"2001","journal-title":"Cell Stress Chaperones"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1379\/1466-1268(2003)008<0348:HSPRIA>2.0.CO;2","article-title":"Heat shock protein 70-reactivity is associated with increased cell surface density of CD94\/CD56 on primary natural killer cells","volume":"8","author":"Gross","year":"2003","journal-title":"Cell Stress Chaperones"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"41173","DOI":"10.1074\/jbc.M302644200","article-title":"Cell surface-bound heat shock protein 70 (Hsp70) mediates perforin-independent apoptosis by specific binding and uptake of granzyme B","volume":"278","author":"Gross","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1038\/onc.2014.63","article-title":"Tumor-derived inducible heat-shock protein 70 (HSP70) is an essential component of anti-tumor immunity","volume":"34","author":"Dodd","year":"2015","journal-title":"Oncogene"},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Wachstein, J., Tischer, S., Figueiredo, C., Limbourg, A., Falk, C., Immenschuh, S., Blasczyk, R., and Eiz-Vesper, B. (2012). HSP70 enhances immunosuppressive function of CD4(+)CD25(+)FoxP3(+) T regulatory cells and cytotoxicity in CD4(+)CD25(-) T cells. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0051747"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"11970","DOI":"10.1158\/0008-5472.CAN-07-2259","article-title":"Induction of hsp70-mediated Th17 autoimmunity can be exploited as immunotherapy for metastatic prostate cancer","volume":"67","author":"Kottke","year":"2007","journal-title":"Cancer Res."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1016\/j.cell.2011.07.033","article-title":"Control of TH17\/Treg Balance by Hypoxia-Inducible Factor 1","volume":"146","author":"Dang","year":"2011","journal-title":"Cell"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.immuni.2020.01.006","article-title":"Febrile Temperature Critically Controls the Differentiation and Pathogenicity of T Helper 17 Cells","volume":"52","author":"Wang","year":"2020","journal-title":"Immunity"},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Cwiklinska, H., Cichalewska-Studzinska, M., Selmaj, K.W., and Mycko, M.P. (2020). The Heat Shock Protein HSP70 Promotes Th17 Genes\u2019 Expression via Specific Regulation of microRNA. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21082823"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"27136","DOI":"10.1038\/srep27136","article-title":"Cryo-thermal therapy elicits potent anti-tumor immunity by inducing extracellular Hsp70-dependent MDSC differentiation","volume":"6","author":"Zhu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1152\/japplphysiol.00658.2012","article-title":"Heat shock protein 70 (Hsp70) inhibits oxidative phosphorylation and compensates ATP balance through enhanced glycolytic activity","volume":"113","author":"Wang","year":"1985","journal-title":"J. Appl. Physiol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1080\/10253890.2019.1568987","article-title":"Regulating glycolysis, the TLR4 signal pathway and expression of RBM3 in mouse liver in response to acute cold exposure","volume":"22","author":"Shi","year":"2019","journal-title":"Stress"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"361","DOI":"10.2337\/db18-0035","article-title":"HSPA12A Is a Novel Player in Nonalcoholic Steatohepatitis via Promoting Nuclear PKM2-Mediated M1 Macrophage Polarization","volume":"68","author":"Kong","year":"2019","journal-title":"Diabetes"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"16260","DOI":"10.1038\/s41598-019-52545-3","article-title":"Rapid deacetylation of yeast Hsp70 mediates the cellular response to heat stress","volume":"9","author":"Xu","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"493934","DOI":"10.1155\/2012\/493934","article-title":"ER-Mitochondria Crosstalk during Cerebral Ischemia: Molecular Chaperones and ER-Mitochondrial Calcium Transfer","volume":"2012","author":"Ouyang","year":"2012","journal-title":"Int. J. Cell Biol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/s10038-020-0736-8","article-title":"Epigenetic silencing of heat shock protein 70 through DNA hypermethylation in pseudoexfoliation syndrome and glaucoma","volume":"65","author":"Hayat","year":"2020","journal-title":"J. Hum. Genet."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"801","DOI":"10.4161\/cbt.7.6.6281","article-title":"Hsp60 expression, new locations, functions, and perspectives for cancer diagnosis and therapy","volume":"7","author":"Cappello","year":"2008","journal-title":"Cancer Biol. Ther."},{"key":"ref_130","unstructured":"Asea, A.A.A., and Kaur, P. (2019). Hsp60 in Modifications of Nervous System Homeostasis and Neurodegeneration. Heat Shock Protein 60 in Human Diseases and Disorders, Springer International Publishing."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1186\/2193-1801-2-431","article-title":"Hyperglycaemia and oxidative stress upregulate HSP60 & HSP70 expression in HeLa cells","volume":"2","author":"Hall","year":"2013","journal-title":"Springerplus"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1007\/s12192-017-0858-x","article-title":"Endothelial TNF-\u03b1 induction by Hsp60 secreted from THP-1 monocytes exposed to hyperglycaemic conditions","volume":"23","author":"Martinus","year":"2018","journal-title":"Cell Stress Chaperones"},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Liyanagamage, D., and Martinus, R.D. (2020). Role of Mitochondrial Stress Protein HSP60 in Diabetes-Induced Neuroinflammation. Mediat. Inflamm., 17.","DOI":"10.1155\/2020\/8073516"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"3212","DOI":"10.4049\/jimmunol.162.6.3212","article-title":"Human 60-kDa Heat-Shock Protein: A Danger Signal to the Innate Immune System","volume":"162","author":"Chen","year":"1999","journal-title":"J. Immunol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"2340","DOI":"10.4049\/jimmunol.170.5.2340","article-title":"Human Heat Shock Protein 60 Induces Maturation of Dendritic Cells Versus a Th1-Promoting Phenotype","volume":"170","author":"Lendemans","year":"2003","journal-title":"J. Immunol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"13","DOI":"10.4049\/jimmunol.164.1.13","article-title":"Cutting Edge: Heat Shock Protein (HSP) 60 Activates the Innate Immune Response: CD14 Is an Essential Receptor for HSP60 Activation of Mononuclear Cells","volume":"164","author":"Kol","year":"2000","journal-title":"J. Immunol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"4669","DOI":"10.1074\/jbc.M608666200","article-title":"Synergistic and Differential Modulation of Immune Responses by Hsp60 and Lipopolysaccharide","volume":"282","author":"Osterloh","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"2051","DOI":"10.1002\/1521-4141(200107)31:7<2051::AID-IMMU2051>3.0.CO;2-H","article-title":"Heat shock proteins as \u2019danger signals\u2019: Eukaryotic Hsp60 enhances and accelerates antigen-specific IFN-\u03b3\u2009 production in T cells","volume":"31","author":"Breloer","year":"2001","journal-title":"Eur. J. Immunol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"2022","DOI":"10.1172\/JCI28423","article-title":"Heat shock protein 60 enhances CD4+ CD25+ regulatory T cell function via innate TLR2 signaling","volume":"116","author":"Cahalon","year":"2006","journal-title":"J. Clin. Investig."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.it.2010.11.001","article-title":"The HSP60 immune system network","volume":"32","author":"Quintana","year":"2011","journal-title":"Trends Immunol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1038\/nri1593","article-title":"Heat-shock proteins induce T-cell regulation of chronic inflammation","volume":"5","author":"Prakken","year":"2005","journal-title":"Nat. Rev. Immunol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.1002\/art.11174","article-title":"The spontaneous remission of juvenile idiopathic arthritis is characterized by CD30+ T cells directed to human heat-shock protein 60 capable of producing the regulatory cytokine interleukin-10","volume":"48","author":"Kamphuis","year":"2003","journal-title":"Arthritis Rheum."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"019","DOI":"10.1038\/s41598-019-48992-7","article-title":"HSP60-regulated Mitochondrial Proteostasis and Protein Translation Promote Tumor Growth of Ovarian Cancer","volume":"9","author":"Guo","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_144","first-page":"017","article-title":"Oncogenic HSP60 regulates mitochondrial oxidative phosphorylation to support Erk1\/2 activation during pancreatic cancer cell growth","volume":"9","author":"Zhou","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.redox.2019.101218","article-title":"HSP60 silencing promotes Warburg-like phenotypes and switches the mitochondrial function from ATP production to biosynthesis in ccRCC cells","volume":"24","author":"Teng","year":"2019","journal-title":"Redox Biol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"2560","DOI":"10.1007\/s00018-006-6192-6","article-title":"The diversity of the DnaJ\/Hsp40 family, the crucial partners for Hsp70 chaperones","volume":"63","author":"Qiu","year":"2006","journal-title":"Cell. Mol. Life Sci. CMLS"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1379\/1466-1268(2003)008<0309:MFROHF>2.0.CO;2","article-title":"Mechanisms for regulation of Hsp70 function by Hsp40","volume":"8","author":"Fan","year":"2003","journal-title":"Cell Stress Chaperones"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1128\/IAI.72.3.1364-1373.2004","article-title":"The DnaK\/DnaJ chaperone machinery of Salmonella enterica serovar Typhimurium is essential for invasion of epithelial cells and survival within macrophages, leading to systemic infection","volume":"72","author":"Takaya","year":"2004","journal-title":"Infect. Immun."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.molimm.2017.01.021","article-title":"DnaJ (hsp40) of Streptococcus pneumoniae is involved in bacterial virulence and elicits a strong natural immune reaction via PI3K\/JNK","volume":"83","author":"Cui","year":"2017","journal-title":"Mol. Immunol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"6225","DOI":"10.1016\/j.vaccine.2006.05.074","article-title":"Immunogenicity and protective efficacy of DnaJ (hsp40) of Streptococcus pneumoniae against lethal infection in mice","volume":"24","author":"Khan","year":"2006","journal-title":"Vaccine"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1016\/j.vaccine.2010.12.126","article-title":"Immunization with DnaJ (hsp40) could elicit protection against nasopharyngeal colonization and invasive infection caused by different strains of Streptococcus pneumoniae","volume":"29","author":"Cui","year":"2011","journal-title":"Vaccine"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1007\/s12192-010-0168-z","article-title":"Hsp40 proteins modulate humoral and cellular immune response in rheumatoid arthritis patients","volume":"15","author":"Tukaj","year":"2010","journal-title":"Cell Stress Chaperones"},{"key":"ref_153","doi-asserted-by":"crossref","unstructured":"Huang, L., Yu, Z., Zhang, T., Zhao, X., and Huang, G. (2014). HSP40 interacts with pyruvate kinase M2 and regulates glycolysis and cell proliferation in tumor cells. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0092949"},{"key":"ref_154","first-page":"562","article-title":"Tazarotene-Induced Gene 1 Interacts with DNAJC8 and Regulates Glycolysis in Cervical Cancer Cells","volume":"41","author":"Wang","year":"2018","journal-title":"Mol. Cells"},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Webster, J.M., Darling, A.L., Uversky, V.N., and Blair, L.J. (2019). Small Heat Shock Proteins, Big Impact on Protein Aggregation in Neurodegenerative Disease. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.01047"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1038\/nsmb993","article-title":"Some like it hot: The structure and function of small heat-shock proteins","volume":"12","author":"Haslbeck","year":"2005","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.yjmcc.2004.12.014","article-title":"Small heat shock proteins: A new classification scheme in mammals","volume":"38","author":"Taylor","year":"2005","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1038\/nature05935","article-title":"Protective and therapeutic role for \u03b1B-crystallin in autoimmune demyelination","volume":"448","author":"Ousman","year":"2007","journal-title":"Nature"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1038\/s41385-019-0198-5","article-title":"Small heat shock protein CRYAB inhibits intestinal mucosal inflammatory responses and protects barrier integrity through suppressing IKK\u03b2 activity","volume":"12","author":"Xu","year":"2019","journal-title":"Mucosal. Immunol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1016\/j.biocel.2011.12.010","article-title":"The link between small heat shock proteins and the immune system","volume":"44","author":"Bsibsi","year":"2012","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1097\/NEN.0b013e3181e4939c","article-title":"\u03b1B-Crystallin Is a Target for Adaptive Immune Responses and a Trigger of Innate Responses in Preactive Multiple Sclerosis Lesions","volume":"69","author":"Bsibsi","year":"2010","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1016\/j.jmb.2008.07.068","article-title":"Selective Cu2+ binding, redox silencing, and cytoprotective effects of the small heat shock proteins alphaA- and alphaB-crystallin","volume":"382","author":"Ahmad","year":"2008","journal-title":"J. Mol. Biol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1042\/BJ20050506","article-title":"\u03b1B-crystallin-assisted reactivation of glucose-6-phosphate dehydrogenase upon refolding","volume":"391","author":"Kumar","year":"2005","journal-title":"Biochem. J."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"3951","DOI":"10.4049\/jimmunol.165.7.3951","article-title":"Exaggerated Human Monocyte IL-10 Concomitant to Minimal TNF-\u03b1 Induction by Heat-Shock Protein 27 (Hsp27) Suggests Hsp27 Is Primarily an Antiinflammatory Stimulus","volume":"165","author":"De","year":"2000","journal-title":"J. Immunol."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"2812","DOI":"10.1002\/eji.200636993","article-title":"Exogenous heat shock protein\u200427 uniquely blocks differentiation of monocytes to dendritic cells","volume":"37","author":"Laudanski","year":"2007","journal-title":"Eur. J. Immunol."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"675","DOI":"10.4049\/jimmunol.182.1.675","article-title":"Heat shock proteins HSP27 and HSP70 are present in the skin and are important mediators of allergic contact hypersensitivity","volume":"182","author":"Yusuf","year":"2009","journal-title":"J. Immunol."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/s12192-012-0356-0","article-title":"Extracellular HSP27 acts as a signaling molecule to activate NF-\u03baB in macrophages","volume":"18","author":"Salari","year":"2013","journal-title":"Cell Stress Chaperones"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.tcm.2010.03.008","article-title":"Heat shock protein 27: Clue to understanding estrogen-mediated atheroprotection?","volume":"20","author":"Rayner","year":"2010","journal-title":"Trends Cardiovasc. Med."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1016\/j.immuni.2018.08.021","article-title":"Cholesterol Homeostatic Regulator SCAP-SREBP2 Integrates NLRP3 Inflammasome Activation and Cholesterol Biosynthetic Signaling in Macrophages","volume":"49","author":"Guo","year":"2018","journal-title":"Immunity"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1038\/nature08938","article-title":"NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals","volume":"464","author":"Duewell","year":"2010","journal-title":"Nature"},{"key":"ref_171","doi-asserted-by":"crossref","unstructured":"Chopra, S., Giovanelli, P., Alvarado-Vazquez, P.A., Alonso, S., Song, M., Sandoval, T.A., Chae, C.S., Tan, C., Fonseca, M.M., and Gutierrez, S. (2019). IRE1\u03b1-XBP1 signaling in leukocytes controls prostaglandin biosynthesis and pain. Science, 365.","DOI":"10.1126\/science.aau6499"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"2695","DOI":"10.1002\/j.1460-2075.1996.tb00630.x","article-title":"Human hsp27, Drosophila hsp27 and human alphaB-crystallin expression-mediated increase in glutathione is essential for the protective activity of these proteins against TNFalpha-induced cell death","volume":"15","author":"Mehlen","year":"1996","journal-title":"EMBO J."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.yjmcc.2006.03.003","article-title":"CRYAB and HSPB2 deficiency increases myocyte mitochondrial permeability transition and mitochondrial calcium uptake","volume":"40","author":"Kadono","year":"2006","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1007\/s12192-012-0335-5","article-title":"Protein refolding in peroxisomes is dependent upon an HSF1-regulated function","volume":"17","author":"Heldens","year":"2012","journal-title":"Cell Stress Chaperones"},{"key":"ref_175","doi-asserted-by":"crossref","unstructured":"Wanders, R.J.A., Waterham, H.R., and Ferdinandusse, S. (2016). Metabolic Interplay between Peroxisomes and Other Subcellular Organelles Including Mitochondria and the Endoplasmic Reticulum. Front. Cell Dev. Biol., 3.","DOI":"10.3389\/fcell.2015.00083"},{"key":"ref_176","doi-asserted-by":"crossref","unstructured":"Yarosz, E.L., and Chang, C.H. (2018). The Role of Reactive Oxygen Species in Regulating T Cell-mediated Immunity and Disease. Immune. Netw., 18.","DOI":"10.4110\/in.2018.18.e14"},{"key":"ref_177","doi-asserted-by":"crossref","unstructured":"Batista-Gonzalez, A., Vidal, R., Criollo, A., and Carre\u00f1o, L.J. (2020). New Insights on the Role of Lipid Metabolism in the Metabolic Reprogramming of Macrophages. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.02993"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"2657","DOI":"10.1172\/JCI97943","article-title":"Resolvins in inflammation: Emergence of the pro-resolving superfamily of mediators","volume":"128","author":"Serhan","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_179","doi-asserted-by":"crossref","unstructured":"Di Cara, F., Andreoletti, P., Trompier, D., Vejux, A., B\u00fclow, M.H., Sellin, J., Lizard, G., Cherkaoui-Malki, M., and Savary, S. (2019). Peroxisomes in Immune Response and Inflammation. Int. J. Mol. Sci, 20.","DOI":"10.3390\/ijms20163877"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.cell.2015.02.019","article-title":"Cholesterol transport through lysosome-peroxisome membrane contacts","volume":"161","author":"Chu","year":"2015","journal-title":"Cell"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.cmet.2019.04.002","article-title":"Cholesterol Induces CD8(+) T Cell Exhaustion in the Tumor Microenvironment","volume":"30","author":"Ma","year":"2019","journal-title":"Cell Metab."},{"key":"ref_182","first-page":"9","article-title":"Role of peroxisomes in ROS\/RNS-metabolism: Implications for human disease","volume":"9","author":"Fransen","year":"2012","journal-title":"Biochim. Biophys. Acta."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1016\/j.immuni.2018.03.035","article-title":"Peroxisome-Mediated Metabolism Is Required for Immune Response to Microbial Infection","volume":"48","author":"Sheshachalam","year":"2018","journal-title":"Immunity"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1007\/s12192-017-0856-z","article-title":"Extracellular small heat shock proteins: Exosomal biogenesis and function","volume":"23","author":"Reddy","year":"2018","journal-title":"Cell Stress Chaperones"},{"key":"ref_185","doi-asserted-by":"crossref","unstructured":"Taha, E.A., Ono, K., and Eguchi, T. (2019). Roles of Extracellular HSPs as Biomarkers in Immune Surveillance and Immune Evasion. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20184588"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1097\/SHK.0b013e3182a185ab","article-title":"Extracellular heat shock proteins: A new location, a new function","volume":"40","author":"Vazquez","year":"2013","journal-title":"Shock"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"755","DOI":"10.4049\/jimmunol.1203286","article-title":"Immunotherapy of radioresistant mammary tumors with early metastasis using molecular chaperone vaccines combined with ionizing radiation","volume":"191","author":"Weng","year":"2013","journal-title":"J. Immunol."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"488","DOI":"10.4049\/jimmunol.0902255","article-title":"A heat shock protein 70-based vaccine with enhanced immunogenicity for clinical use","volume":"184","author":"Gong","year":"2010","journal-title":"J. Immunol."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/S1074-7613(02)00388-6","article-title":"Involvement of LOX-1 in dendritic cell-mediated antigen cross-presentation","volume":"17","author":"Delneste","year":"2002","journal-title":"Immunity"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1038\/s41419-018-1279-1","article-title":"Pro-oncogenic action of LOX-1 and its splice variant LOX-1\u03944 in breast cancer phenotypes","volume":"10","author":"Pucci","year":"2019","journal-title":"Cell Death. Dis."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"3110","DOI":"10.1161\/01.CIR.99.24.3110","article-title":"Expression of lectinlike oxidized low-density lipoprotein receptor-1 in human atherosclerotic lesions","volume":"99","author":"Kataoka","year":"1999","journal-title":"Circulation"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"3344","DOI":"10.1128\/MCB.01287-07","article-title":"Transforming growth factor alpha (TGFalpha)-stimulated secretion of HSP90alpha: Using the receptor LRP-1\/CD91 to promote human skin cell migration against a TGFbeta-rich environment during wound healing","volume":"28","author":"Cheng","year":"2008","journal-title":"Mol. Cell Biol."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"25458","DOI":"10.1074\/jbc.M110.139345","article-title":"Secreted heat shock protein 90alpha induces colorectal cancer cell invasion through CD91\/LRP-1 and NF-kappaB-mediated integrin alphaV expression","volume":"285","author":"Chen","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1084\/jem.194.6.781","article-title":"C1q and mannose binding lectin engagement of cell surface calreticulin and CD91 initiates macropinocytosis and uptake of apoptotic cells","volume":"194","author":"Ogden","year":"2001","journal-title":"J. Exp. Med."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1172\/jci.insight.127239","article-title":"CD91 on dendritic cells governs immunosurveillance of nascent, emerging tumors","volume":"4","author":"Sedlacek","year":"2019","journal-title":"JCI Insight."},{"key":"ref_196","doi-asserted-by":"crossref","unstructured":"Pawaria, S., and Binder, R.J. (2011). CD91-dependent programming of T-helper cell responses following heat shock protein immunization. Nat. Commun., 2.","DOI":"10.1038\/ncomms1524"},{"key":"ref_197","doi-asserted-by":"crossref","unstructured":"Actis Dato, V., and Chiabrando, G.A. (2018). The Role of Low-Density Lipoprotein Receptor-Related Protein 1 in Lipid Metabolism, Glucose Homeostasis and Inflammation. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19061780"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1146\/annurev-immunol-032414-112116","article-title":"Endoplasmic reticulum stress in immunity","volume":"33","author":"Bettigole","year":"2015","journal-title":"Annu. Rev. Immunol."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/j.cmet.2014.01.011","article-title":"Mitohormesis","volume":"19","author":"Yun","year":"2014","journal-title":"Cell Metab."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"eaaq1380","DOI":"10.1126\/scisignal.aaq1380","article-title":"ER-mitochondria cross-talk is regulated by the Ca(2+) sensor NCS1 and is impaired in Wolfram syndrome","volume":"11","author":"Angebault","year":"2018","journal-title":"Sci. Signal."},{"key":"ref_201","first-page":"24","article-title":"Cancer and ER stress: Mutual crosstalk between autophagy, oxidative stress and inflammatory response","volume":"118","author":"Lin","year":"2019","journal-title":"Biomed. Pharmacother. Biomed. Pharmacother."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ceca.2017.01.003","article-title":"The endoplasmic reticulum-mitochondria coupling in health and disease: Molecules, functions and significance","volume":"62","author":"Filadi","year":"2017","journal-title":"Cell Calcium"}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/10\/10\/394\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:16:21Z","timestamp":1760177781000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/10\/10\/394"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,3]]},"references-count":202,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2020,10]]}},"alternative-id":["metabo10100394"],"URL":"https:\/\/doi.org\/10.3390\/metabo10100394","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,3]]}}}