{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T00:05:52Z","timestamp":1793664352125,"version":"4.5.1"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T00:00:00Z","timestamp":1750032000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T00:00:00Z","timestamp":1750032000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82272201"],"award-info":[{"award-number":["82272201"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100022963","name":"Key Research and Development Program of Zhejiang Province","doi-asserted-by":"publisher","award":["2021C03072"],"award-info":[{"award-number":["2021C03072"]}],"id":[{"id":"10.13039\/100022963","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007452","name":"Wu Jieping Medical Foundation","doi-asserted-by":"publisher","award":["320.6750.2022-26-16"],"award-info":[{"award-number":["320.6750.2022-26-16"]}],"id":[{"id":"10.13039\/100007452","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Commun Signal"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Lipid metabolic reprogramming is a key feature of sepsis, with increased lipid storage contributing to disease progression. Although lipid metabolism dysregulation has been implicated in sepsis pathogenesis, how lipid biosynthesis, particularly mediated by sterol regulatory element-binding transcription factor 1 (SREBF1), leads to dendritic cell (DC) immunoparalysis remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Intracellular lipid accumulation was assessed by Oil Red O and BODIPY staining. Gene and protein expression levels were analyzed via qPCR, Western blot, and immunofluorescence. SREBF1 activity was modulated using genetic knockout and siRNA silencing. DC phenotype and CD4\n                      <jats:sup>+<\/jats:sup>\n                      \u2009T cell proliferation were evaluated using flow cytometry and co-culture assays. Cytokine secretion was measured using ELISA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In a cecal ligation and puncture-induced sepsis model, we observed increased lipid biosynthesis and significantly elevated SREBF1 expression in spleen DCs. Increased SREBF1 expression suppressed the expression of costimulatory molecules (e.g., CD40, CD80, and CD86) and MHC II, reduced the secretion of inflammatory cytokines (e.g., TNF\u03b1, IL-1\u03b2, IL-6, and IL-12), impaired CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cell activation, and promoted apoptosis. Mechanistically, SREBF1 activation enhanced lipid biosynthesis in DCs, which triggered endoplasmic reticulum (ER) stress, as evidenced by increased PERK phosphorylation, eIF2\u03b1 activation, and subsequent ATF4\/CHOP induction. SREBF1 silencing attenuated the lipid-induced ER stress and restored DC function, whereas tunicamycin treatment partially reversed these protective effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study identifies SREBF1 as a central regulator of sepsis-induced DC immunoparalysis by coupling lipid metabolic reprogramming to ER stress activation. Targeting this SREBF1-lipid-ER stress axis represents a novel strategy to reverse immunosuppression in septic patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12964-025-02295-9","type":"journal-article","created":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T09:29:55Z","timestamp":1750066195000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["SREBF1 mediates immunoparalysis of dendritic cells in sepsis by regulating lipid metabolism and endoplasmic reticulum stress"],"prefix":"10.1186","volume":"23","author":[{"given":"Yaolu","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangfang","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liuyan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongqiu","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,16]]},"reference":[{"issue":"8","key":"2295_CR1","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1001\/jama.2016.0287","volume":"315","author":"M Singer","year":"2016","unstructured":"Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The third international consensus definitions for Sepsis and septic shock (Sepsis-3). JAMA. 2016;315(8):801\u201310.","journal-title":"JAMA"},{"issue":"2","key":"2295_CR2","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1038\/nrneph.2017.165","volume":"14","author":"F Venet","year":"2018","unstructured":"Venet F, Monneret G. Advances in the Understanding and treatment of sepsis-induced immunosuppression. Nat Rev Nephrol. 2018;14(2):121\u201337.","journal-title":"Nat Rev Nephrol"},{"issue":"1","key":"2295_CR3","first-page":"56","volume":"9","author":"D Liu","year":"2022","unstructured":"Liu D, Huang SY, Sun JH, Zhang HC, Cai QL, Gao C, et al. Sepsis-induced immunosuppression: mechanisms, diagnosis and current treatment options. Mil Med Res. 2022;9(1):56.","journal-title":"Mil Med Res"},{"key":"2295_CR4","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.cytogfr.2022.07.007","volume":"69","author":"W Zhang","year":"2023","unstructured":"Zhang W, Fang X, Gao C, Song C, He Y, Zhou T, et al. MDSCs in sepsis-induced immunosuppression and its potential therapeutic targets. Cytokine Growth Factor Rev. 2023;69:90\u2013103.","journal-title":"Cytokine Growth Factor Rev"},{"key":"2295_CR5","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1146\/annurev-physiol-061121-040214","volume":"84","author":"LK Torres","year":"2022","unstructured":"Torres LK, Pickkers P, van der Poll T. Sepsis-Induced immunosuppression. Annu Rev Physiol. 2022;84:157\u201381.","journal-title":"Annu Rev Physiol"},{"key":"2295_CR6","doi-asserted-by":"publisher","first-page":"i2375","DOI":"10.1136\/bmj.i2375","volume":"353","author":"HC Prescott","year":"2016","unstructured":"Prescott HC, Osterholzer JJ, Langa KM, Angus DC, Iwashyna TJ. Late mortality after sepsis: propensity matched cohort study. BMJ. 2016;353:i2375.","journal-title":"BMJ"},{"issue":"1","key":"2295_CR7","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1038\/cr.2016.157","volume":"27","author":"RL Sabado","year":"2017","unstructured":"Sabado RL, Balan S, Bhardwaj N. Dendritic cell-based immunotherapy. Cell Res. 2017;27(1):74\u201395.","journal-title":"Cell Res"},{"issue":"4","key":"2295_CR8","doi-asserted-by":"publisher","first-page":"R119","DOI":"10.1186\/cc7969","volume":"13","author":"H Poehlmann","year":"2009","unstructured":"Poehlmann H, Schefold JC, Zuckermann-Becker H, Volk HD, Meisel C. Phenotype changes and impaired function of dendritic cell subsets in patients with sepsis: a prospective observational analysis. Crit Care. 2009;13(4):R119.","journal-title":"Crit Care"},{"issue":"12","key":"2295_CR9","doi-asserted-by":"publisher","first-page":"e13328","DOI":"10.1111\/cpr.13328","volume":"55","author":"Q Tu","year":"2022","unstructured":"Tu Q, Li Y, Zhu J, Guo L, Liu C, Liu L, et al. Mitochondrial DNA mediates immunoparalysis of dendritic cells in sepsis via STING signalling. Cell Prolif. 2022;55(12):e13328.","journal-title":"Cell Prolif"},{"key":"2295_CR10","doi-asserted-by":"publisher","first-page":"775","DOI":"10.3389\/fimmu.2019.00775","volume":"10","author":"SK Wculek","year":"2019","unstructured":"Wculek SK, Khouili SC, Priego E, Heras-Murillo I, Sancho D. Metabolic control of dendritic cell functions: digesting information. Front Immunol. 2019;10:775.","journal-title":"Front Immunol"},{"key":"2295_CR11","doi-asserted-by":"publisher","first-page":"152","DOI":"10.3389\/fcell.2018.00152","volume":"6","author":"X Du","year":"2018","unstructured":"Du X, Chapman NM, Chi H. Emerging roles of cellular metabolism in regulating dendritic cell subsets and function. Front Cell Dev Biol. 2018;6:152.","journal-title":"Front Cell Dev Biol"},{"issue":"1","key":"2295_CR12","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1084\/jem.20151570","volume":"213","author":"LA O\u2019Neill","year":"2016","unstructured":"O\u2019Neill LA, Pearce EJ. Immunometabolism governs dendritic cell and macrophage function. J Exp Med. 2016;213(1):15\u201323.","journal-title":"J Exp Med"},{"issue":"4","key":"2295_CR13","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1053\/j.gastro.2012.06.003","volume":"143","author":"J Ibrahim","year":"2012","unstructured":"Ibrahim J, Nguyen AH, Rehman A, Ochi A, Jamal M, Graffeo CS, et al. Dendritic cell populations with different concentrations of lipid regulate tolerance and immunity in mouse and human liver. Gastroenterology. 2012;143(4):1061\u201372.","journal-title":"Gastroenterology"},{"issue":"8","key":"2295_CR14","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1038\/nm.2172","volume":"16","author":"DL Herber","year":"2010","unstructured":"Herber DL, Cao W, Nefedova Y, Novitskiy SV, Nagaraj S, Tyurin VA, et al. Lipid accumulation and dendritic cell dysfunction in cancer. Nat Med. 2010;16(8):880\u20136.","journal-title":"Nat Med"},{"key":"2295_CR15","doi-asserted-by":"publisher","first-page":"2927","DOI":"10.3389\/fimmu.2018.02927","volume":"9","author":"L Jiang","year":"2018","unstructured":"Jiang L, Fang X, Wang H, Li D, Wang X. Ovarian Cancer-Intrinsic fatty acid synthase prevents Anti-tumor immunity by disrupting Tumor-Infiltrating dendritic cells. Front Immunol. 2018;9:2927.","journal-title":"Front Immunol"},{"issue":"9","key":"2295_CR16","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1172\/JCI0215593","volume":"109","author":"JD Horton","year":"2002","unstructured":"Horton JD, Goldstein JL, Brown MS. SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest. 2002;109(9):1125\u201331.","journal-title":"J Clin Invest"},{"issue":"3","key":"2295_CR17","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/S0092-8674(00)80213-5","volume":"89","author":"MS Brown","year":"1997","unstructured":"Brown MS, Goldstein JL. The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. Cell. 1997;89(3):331\u201340.","journal-title":"Cell"},{"issue":"5","key":"2295_CR18","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1016\/j.cmet.2011.04.001","volume":"13","author":"SS Im","year":"2011","unstructured":"Im SS, Yousef L, Blaschitz C, Liu JZ, Edwards RA, Young SG, et al. Linking lipid metabolism to the innate immune response in macrophages through sterol regulatory element binding protein-1a. Cell Metab. 2011;13(5):540\u20139.","journal-title":"Cell Metab"},{"issue":"9","key":"2295_CR19","doi-asserted-by":"publisher","first-page":"1150","DOI":"10.1038\/s42255-021-00440-5","volume":"3","author":"G Bidault","year":"2021","unstructured":"Bidault G, Virtue S, Petkevicius K, Jolin HE, Dugourd A, Gu\u00e9nantin AC, et al. SREBP1-induced fatty acid synthesis depletes macrophages antioxidant defences to promote their alternative activation. Nat Metab. 2021;3(9):1150\u201362.","journal-title":"Nat Metab"},{"issue":"1","key":"2295_CR20","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1038\/nprot.2008.214","volume":"4","author":"D Rittirsch","year":"2009","unstructured":"Rittirsch D, Huber-Lang MS, Flierl MA, Ward PA. Immunodesign of experimental sepsis by cecal ligation and puncture. Nat Protoc. 2009;4(1):31\u20136.","journal-title":"Nat Protoc"},{"issue":"1","key":"2295_CR21","doi-asserted-by":"publisher","first-page":"1898","DOI":"10.1038\/s41467-019-09903-6","volume":"10","author":"H Wang","year":"2019","unstructured":"Wang H, Hu X, Huang M, Liu J, Gu Y, Ma L, et al. Mettl3-mediated mRNA m(6)A methylation promotes dendritic cell activation. Nat Commun. 2019;10(1):1898.","journal-title":"Nat Commun"},{"issue":"3","key":"2295_CR22","doi-asserted-by":"publisher","first-page":"108278","DOI":"10.1016\/j.celrep.2020.108278","volume":"33","author":"X Yin","year":"2020","unstructured":"Yin X, Zeng W, Wu B, Wang L, Wang Z, Tian H, et al. PPAR\u03b1 Inhibition overcomes Tumor-Derived Exosomal Lipid-Induced dendritic cell dysfunction. Cell Rep. 2020;33(3):108278.","journal-title":"Cell Rep"},{"issue":"7564","key":"2295_CR23","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1038\/nature14557","volume":"524","author":"J Han","year":"2015","unstructured":"Han J, Li E, Chen L, Zhang Y, Wei F, Liu J, et al. The CREB coactivator CRTC2 controls hepatic lipid metabolism by regulating SREBP1. Nature. 2015;524(7564):243\u20136.","journal-title":"Nature"},{"issue":"21","key":"2295_CR24","doi-asserted-by":"publisher","first-page":"12027","DOI":"10.1073\/pnas.1534923100","volume":"100","author":"JD Horton","year":"2003","unstructured":"Horton JD, Shah NA, Warrington JA, Anderson NN, Park SW, Brown MS, Goldstein JL. Combined analysis of oligonucleotide microarray data from Transgenic and knockout mice identifies direct SREBP target genes. Proc Natl Acad Sci U S A. 2003;100(21):12027\u201332.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"36","key":"2295_CR25","doi-asserted-by":"publisher","first-page":"34259","DOI":"10.1074\/jbc.M103848200","volume":"276","author":"Y Ikeda","year":"2001","unstructured":"Ikeda Y, Yamamoto J, Okamura M, Fujino T, Takahashi S, Takeuchi K, et al. Transcriptional regulation of the murine acetyl-CoA synthetase 1 gene through multiple clustered binding sites for sterol regulatory element-binding proteins and a single neighboring site for Sp1. J Biol Chem. 2001;276(36):34259\u201369.","journal-title":"J Biol Chem"},{"issue":"52","key":"2295_CR26","doi-asserted-by":"publisher","first-page":"E12228","DOI":"10.1073\/pnas.1813458115","volume":"115","author":"JH Lee","year":"2018","unstructured":"Lee JH, Phelan P, Shin M, Oh BC, Han X, Im SS, Osborne TF. SREBP-1a-stimulated lipid synthesis is required for macrophage phagocytosis downstream of TLR4-directed mTORC1. Proc Natl Acad Sci U S A. 2018;115(52):E12228\u201334.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"12","key":"2295_CR27","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1038\/nrendo.2017.91","volume":"13","author":"H Shimano","year":"2017","unstructured":"Shimano H, Sato R. SREBP-regulated lipid metabolism: convergent physiology - divergent pathophysiology. Nat Rev Endocrinol. 2017;13(12):710\u201330.","journal-title":"Nat Rev Endocrinol"},{"issue":"5","key":"2295_CR28","doi-asserted-by":"publisher","first-page":"e8817","DOI":"10.1016\/j.jcrc.2013.05.007","volume":"28","author":"KI Elsayh","year":"2013","unstructured":"Elsayh KI, Zahran AM, Lotfy Mohamad I, Aly SS. Dendritic cells in childhood sepsis. J Crit Care. 2013;28(5):e8817\u201313.","journal-title":"J Crit Care"},{"issue":"10","key":"2295_CR29","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1038\/s41419-019-2015-1","volume":"10","author":"C Cao","year":"2019","unstructured":"Cao C, Yu M, Chai Y. Pathological alteration and therapeutic implications of sepsis-induced immune cell apoptosis. Cell Death Dis. 2019;10(10):782.","journal-title":"Cell Death Dis"},{"issue":"1","key":"2295_CR30","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1089\/jir.2014.0069","volume":"35","author":"YY Luan","year":"2015","unstructured":"Luan YY, Yao YM, Xiao XZ, Sheng ZY. Insights into the apoptotic death of immune cells in sepsis. J Interferon Cytokine Res. 2015;35(1):17\u201322.","journal-title":"J Interferon Cytokine Res"},{"issue":"6","key":"2295_CR31","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1158\/2159-8290.CD-14-1507","volume":"5","author":"B Qiu","year":"2015","unstructured":"Qiu B, Ackerman D, Sanchez DJ, Li B, Ochocki JD, Grazioli A, et al. HIF2\u03b1-Dependent lipid storage promotes Endoplasmic reticulum homeostasis in Clear-Cell renal cell carcinoma. Cancer Discov. 2015;5(6):652\u201367.","journal-title":"Cancer Discov"},{"issue":"1","key":"2295_CR32","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1186\/s13046-018-0935-8","volume":"37","author":"J Wu","year":"2018","unstructured":"Wu J, Chen S, Liu H, Zhang Z, Ni Z, Chen J, et al. Tunicamycin specifically aggravates ER stress and overcomes chemoresistance in multidrug-resistant gastric cancer cells by inhibiting N-glycosylation. J Exp Clin Cancer Res. 2018;37(1):272.","journal-title":"J Exp Clin Cancer Res"},{"key":"2295_CR33","doi-asserted-by":"publisher","first-page":"125997","DOI":"10.1016\/j.jhazmat.2021.125997","volume":"417","author":"X Liu","year":"2021","unstructured":"Liu X, Chen Y, Wang H, Wei Y, Yuan Y, Zhou Q, et al. Microglia-derived IL-1\u03b2 promoted neuronal apoptosis through ER stress-mediated signaling pathway PERK\/eIF2\u03b1\/ATF4\/CHOP upon arsenic exposure. J Hazard Mater. 2021;417:125997.","journal-title":"J Hazard Mater"},{"issue":"23","key":"2295_CR34","doi-asserted-by":"publisher","first-page":"2594","DOI":"10.1001\/jama.2011.1829","volume":"306","author":"JS Boomer","year":"2011","unstructured":"Boomer JS, To K, Chang KC, Takasu O, Osborne DF, Walton AH, et al. Immunosuppression in patients who die of sepsis and multiple organ failure. JAMA. 2011;306(23):2594\u2013605.","journal-title":"JAMA"},{"issue":"12","key":"2295_CR35","doi-asserted-by":"publisher","first-page":"862","DOI":"10.1038\/nri3552","volume":"13","author":"RS Hotchkiss","year":"2013","unstructured":"Hotchkiss RS, Monneret G, Payen D. Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy. Nat Rev Immunol. 2013;13(12):862\u201374.","journal-title":"Nat Rev Immunol"},{"issue":"9","key":"2295_CR36","doi-asserted-by":"publisher","first-page":"2024","DOI":"10.1016\/j.immuni.2021.08.005","volume":"54","author":"DC Nascimento","year":"2021","unstructured":"Nascimento DC, Viacava PR, Ferreira RG, Damaceno MA, Pi\u00f1eros AR, Melo PH, et al. Sepsis expands a CD39(+) plasmablast population that promotes immunosuppression via adenosine-mediated Inhibition of macrophage antimicrobial activity. Immunity. 2021;54(9):2024\u2013e418.","journal-title":"Immunity"},{"key":"2295_CR37","doi-asserted-by":"publisher","first-page":"624272","DOI":"10.3389\/fimmu.2020.624272","volume":"11","author":"MA McBride","year":"2020","unstructured":"McBride MA, Patil TK, Bohannon JK, Hernandez A, Sherwood ER, Patil NK. Immune checkpoints: novel therapeutic targets to attenuate Sepsis-Induced immunosuppression. Front Immunol. 2020;11:624272.","journal-title":"Front Immunol"},{"issue":"4","key":"2295_CR38","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1038\/ni.2833","volume":"15","author":"B Everts","year":"2014","unstructured":"Everts B, Amiel E, Huang SC, Smith AM, Chang CH, Lam WY, et al. TLR-driven early glycolytic reprogramming via the kinases TBK1-IKK\u025b supports the anabolic demands of dendritic cell activation. Nat Immunol. 2014;15(4):323\u201332.","journal-title":"Nat Immunol"},{"issue":"5","key":"2295_CR39","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1038\/ni.2570","volume":"14","author":"Y Kidani","year":"2013","unstructured":"Kidani Y, Elsaesser H, Hock MB, Vergnes L, Williams KJ, Argus JP, et al. Sterol regulatory element-binding proteins are essential for the metabolic programming of effector T cells and adaptive immunity. Nat Immunol. 2013;14(5):489\u201399.","journal-title":"Nat Immunol"},{"issue":"3","key":"2295_CR40","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1210\/me.2012-1317","volume":"27","author":"J Mandl","year":"2013","unstructured":"Mandl J, M\u00e9sz\u00e1ros T, B\u00e1nhegyi G, Csala M. Minireview: Endoplasmic reticulum stress: control in protein, lipid, and signal homeostasis. Mol Endocrinol. 2013;27(3):384\u201393.","journal-title":"Mol Endocrinol"},{"issue":"11","key":"2295_CR41","doi-asserted-by":"publisher","first-page":"2348","DOI":"10.1111\/febs.15144","volume":"287","author":"Q Hu","year":"2020","unstructured":"Hu Q, Mao Y, Liu M, Luo R, Jiang R, Guo F. The active nuclear form of SREBP1 amplifies ER stress and autophagy via regulation of PERK. Febs J. 2020;287(11):2348\u201366.","journal-title":"Febs J"},{"issue":"7","key":"2295_CR42","doi-asserted-by":"publisher","first-page":"1527","DOI":"10.1016\/j.cell.2015.05.025","volume":"161","author":"JR Cubillos-Ruiz","year":"2015","unstructured":"Cubillos-Ruiz JR, Silberman PC, Rutkowski MR, Chopra S, Perales-Puchalt A, Song M, et al. ER stress sensor XBP1 controls Anti-tumor immunity by disrupting dendritic cell homeostasis. Cell. 2015;161(7):1527\u201338.","journal-title":"Cell"},{"issue":"6","key":"2295_CR43","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1042\/BC20100144","volume":"103","author":"I Hapala","year":"2011","unstructured":"Hapala I, Marza E, Ferreira T. Is fat so bad? Modulation of Endoplasmic reticulum stress by lipid droplet formation. Biol Cell. 2011;103(6):271\u201385.","journal-title":"Biol Cell"},{"issue":"24","key":"2295_CR44","doi-asserted-by":"publisher","first-page":"8209","DOI":"10.1007\/s00018-021-03970-z","volume":"78","author":"LX Wang","year":"2021","unstructured":"Wang LX, Ren C, Yao RQ, Luo YN, Yin Y, Wu Y, et al. Sestrin2 protects against lethal sepsis by suppressing the pyroptosis of dendritic cells. Cell Mol Life Sci. 2021;78(24):8209\u201327.","journal-title":"Cell Mol Life Sci"}],"container-title":["Cell Communication and Signaling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12964-025-02295-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12964-025-02295-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12964-025-02295-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T11:02:47Z","timestamp":1750071767000},"score":1,"resource":{"primary":{"URL":"https:\/\/biosignaling.biomedcentral.com\/articles\/10.1186\/s12964-025-02295-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,16]]},"references-count":44,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["2295"],"URL":"https:\/\/doi.org\/10.1186\/s12964-025-02295-9","relation":{},"ISSN":["1478-811X"],"issn-type":[{"value":"1478-811X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,16]]},"assertion":[{"value":"2 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 June 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 June 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was approved by the Ethics Committee of the First Affiliated Hospital of Wenzhou Medical University (Approval No. KY2024-R191). Written informed consent was obtained from all human participants or their legal guardians prior to sample collection and data analysis. All procedures involving human participants were conducted in accordance with the ethical standards of the Declaration of Helsinki. All animal experiments were approved by the Institutional Animal Care and Use Committee of the First Affiliated Hospital of the Wenzhou Medical University (Approval No. WYYY-AEC-2022-050).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"286"}}