{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T00:28:26Z","timestamp":1759364906113,"version":"build-2065373602"},"reference-count":87,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,28]],"date-time":"2025-09-28T00:00:00Z","timestamp":1759017600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"crossref","award":["JP22K15441","JP25K00292","JP23K18212","JP25K09953"],"award-info":[{"award-number":["JP22K15441","JP25K00292","JP23K18212","JP25K09953"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["IJMS"],"abstract":"<jats:p>Tumor necrosis factor receptor-associated factors (TRAFs) are a family of adaptor proteins that transmit signals from immunoregulatory receptors\u2014such as TNF receptors, Toll-like receptors, and interleukin receptors\u2014to coordinate immune and inflammatory responses. Among them, TRAF5 is highly expressed in lymphocytes and implicated in obesity-associated inflammation, but its role in secondary lymphoid organs during chronic low-grade inflammation remains unclear. We examined splenic B and T cell phenotypes in wild-type (WT) and Traf5-deficient (KO) mice fed a high-fat diet (HFD). Although lymphocyte composition was broadly comparable, KO mice showed reduced spontaneous immunoglobulin G2c (IgG2c) production ex vivo\u2014about 1.5-fold lower than WT. Notably, despite elevated TNF-\u03b1 and CD40 ligand (CD40L) expression in HFD-fed KO splenocytes, IgG2c production remained diminished\u2014about 1.9-fold lower than WT\u2014upon soluble CD40L stimulation, indicating impaired CD40-mediated class-switch recombination (CSR). Consistently, B cells from KO mice on a normal diet exhibited reduced activation-induced cytidine deaminase (AID) expression\u2014about 4.4-fold lower than WT\u2014after CD40L stimulation, and decreased IgG2c secretion\u2014about 6.6-fold lower\u2014upon CD40L and IFN-\u03b3 co-stimulation in vitro. Collectively, these findings suggest that TRAF5 is involved in CD40-dependent CSR in B cells under inflammatory conditions and may contribute to sustaining adaptive immune responses during obesity-associated chronic inflammation.<\/jats:p>","DOI":"10.3390\/ijms26199494","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T15:38:55Z","timestamp":1759246735000},"page":"9494","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Defective IgG Class Switching in the Spleen of TRAF5-Deficient Mice Reveals a Role for TRAF5 in CD40-Mediated B Cell Responses During Obesity-Associated Inflammation"],"prefix":"10.3390","volume":"26","author":[{"given":"Tomomi","family":"Wakaizumi","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Cell Biology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5533-4460","authenticated-orcid":false,"given":"Mari","family":"Hikosaka-Kuniishi","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Cell Biology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yusuke","family":"Ozawa","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Cell Biology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayaka","family":"Sato","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Cell Biology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chieri","family":"Iwata","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Cell Biology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5819-8556","authenticated-orcid":false,"given":"Tsutomu","family":"Wada","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, University of Toyama, Toyama 930-0194, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3057-8674","authenticated-orcid":false,"given":"Toshiyasu","family":"Sasaoka","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, University of Toyama, Toyama 930-0194, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masashi","family":"Morita","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Cell Biology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3004-8526","authenticated-orcid":false,"given":"Takanori","family":"So","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Cell Biology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1093\/intimm\/dxab058","article-title":"The immunological significance of tumor necrosis factor receptor-associated factors (TRAFs)","volume":"34","author":"So","year":"2022","journal-title":"Int. Immunol."},{"key":"ref_2","first-page":"40","article-title":"Role of tumor necrosis factor receptor-associated factor 5 in B- and T-lymphocytes","volume":"3","author":"Ishii","year":"2023","journal-title":"Explor. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Nagashima, H., Ishii, N., and So, T. (2018). Regulation of Interleukin-6 Receptor Signaling by TNF Receptor-Associated Factor 2 and 5 During Differentiation of Inflammatory CD4+ T Cells. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.01986"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1111\/j.1600-065X.2011.01055.x","article-title":"Roles of tumor necrosis factor receptor associated factor 3 (TRAF3) and TRAF5 in immune cell functions","volume":"244","author":"Hildebrand","year":"2011","journal-title":"Immunol. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1007\/978-0-387-70630-6_3","article-title":"Physiological roles and mechanisms of signaling by TRAF2 and TRAF5","volume":"597","author":"Au","year":"2007","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"14661","DOI":"10.1074\/jbc.271.25.14661","article-title":"TRAF5, an activator of NF-kappaB and putative signal transducer for the lymphotoxin-beta receptor","volume":"271","author":"Nakano","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"9437","DOI":"10.1073\/pnas.93.18.9437","article-title":"TRAF5, a novel tumor necrosis factor receptor-associated factor family protein, mediates CD40 signaling","volume":"93","author":"Ishida","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2042","DOI":"10.1074\/jbc.272.4.2042","article-title":"Tumor necrosis factor receptor-associated factor (TRAF) 5 and TRAF2 are involved in CD30-mediated NFkappaB activation","volume":"272","author":"Aizawa","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"14029","DOI":"10.1074\/jbc.272.22.14029","article-title":"Herpesvirus entry mediator, a member of the tumor necrosis factor receptor (TNFR) family, interacts with members of the TNFR-associated factor family and activates the transcription factors NF-kappaB and AP-1","volume":"272","author":"Marsters","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"13471","DOI":"10.1074\/jbc.272.21.13471","article-title":"ATAR, a novel tumor necrosis factor receptor family member, signals through TRAF2 and TRAF5","volume":"272","author":"Hsu","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"5808","DOI":"10.1074\/jbc.273.10.5808","article-title":"Activation of OX40 signal transduction pathways leads to tumor necrosis factor receptor-associated factor (TRAF) 2- and TRAF5-mediated NF-kappaB activation","volume":"273","author":"Kawamata","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"13353","DOI":"10.1074\/jbc.273.21.13353","article-title":"CD27, a member of the tumor necrosis factor receptor superfamily, activates NF-kappaB and stress-activated protein kinase\/c-Jun N-terminal kinase via TRAF2, TRAF5, and NF-kappaB-inducing kinase","volume":"273","author":"Akiba","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"20551","DOI":"10.1074\/jbc.273.32.20551","article-title":"Characterization of the intracellular domain of receptor activator of NF-kappaB (RANK). Interaction with tumor necrosis factor receptor-associated factors and activation of NF-kappab and c-Jun N-terminal kinase","volume":"273","author":"Darnay","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"9803","DOI":"10.1073\/pnas.96.17.9803","article-title":"Targeted disruption of Traf5 gene causes defects in CD40- and CD27-mediated lymphocyte activation","volume":"96","author":"Nakano","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1084\/jem.192.1.137","article-title":"TACI is a TRAF-interacting receptor for TALL-1, a tumor necrosis factor family member involved in B cell regulation","volume":"192","author":"Xia","year":"2000","journal-title":"J. Exp. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"36530","DOI":"10.1074\/jbc.M104837200","article-title":"Critical roles of TRAF2 and TRAF5 in tumor necrosis factor-induced NF-kappa B activation and protection from cell death","volume":"276","author":"Tada","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"8559","DOI":"10.1074\/jbc.M512915200","article-title":"Tumor necrosis factor receptor (TNFR)-associated factor 5 is a critical intermediate of costimulatory signaling pathways triggered by glucocorticoid-induced TNFR in T cells","volume":"281","author":"Esparza","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1038\/ni.1914","article-title":"The transmembrane activator TACI triggers immunoglobulin class switching by activating B cells through the adaptor MyD88","volume":"11","author":"He","year":"2010","journal-title":"Nat. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"129","DOI":"10.4049\/immunohorizons.2000007","article-title":"TRAF5 Deficiency Ameliorates the Severity of Dextran Sulfate Sodium Colitis by Decreasing TRAF2 Expression in Nonhematopoietic Cells","volume":"4","author":"Phung","year":"2020","journal-title":"Immunohorizons"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"642","DOI":"10.4049\/jimmunol.2001358","article-title":"TNF Receptor-Associated Factor 5 Limits IL-27 Receptor Signaling in CD4+ T Lymphocytes","volume":"208","author":"Kawahara","year":"2022","journal-title":"J. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Hikosaka-Kuniishi, M., Iwata, C., Ozawa, Y., Ogawara, S., Wakaizumi, T., Itaya, R., Sunakawa, R., Sato, A., Nagai, H., and Morita, M. (2024). The Role of TNF Receptor-Associated Factor 5 in the Formation of Germinal Centers by B Cells During the Primary Phase of the Immune Response in Mice. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252212331"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4292","DOI":"10.4049\/jimmunol.172.7.4292","article-title":"TNF receptor-associated factor 5 limits the induction of Th2 immune responses","volume":"172","author":"So","year":"2004","journal-title":"J. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1161\/CIRCRESAHA.110.219295","article-title":"TRAF5 deficiency accelerates atherogenesis in mice by increasing inflammatory cell recruitment and foam cell formation","volume":"107","author":"Missiou","year":"2010","journal-title":"Circ. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1038\/ni.2863","article-title":"The adaptor TRAF5 limits the differentiation of inflammatory CD4+ T cells by antagonizing signaling via the receptor for IL-6","volume":"15","author":"Nagashima","year":"2014","journal-title":"Nat. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1002\/jcb.24669","article-title":"Disruption of tumor necrosis factor receptor associated factor 5 exacerbates pressure overload cardiac hypertrophy and fibrosis","volume":"115","author":"Bian","year":"2014","journal-title":"J. Cell Biochem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.jhep.2016.03.006","article-title":"Tumor necrosis factor receptor-associated factor 5 (Traf5) acts as an essential negative regulator of hepatic steatosis","volume":"65","author":"Gao","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"173092","DOI":"10.1016\/j.ejphar.2020.173092","article-title":"TRAF5 protects against myocardial ischemia reperfusion injury via AKT signaling","volume":"878","author":"Xu","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2563","DOI":"10.1161\/ATVBAHA.121.316677","article-title":"Genetic Deficiency of TRAF5 Promotes Adipose Tissue Inflammation and Aggravates Diet-Induced Obesity in Mice","volume":"41","author":"Gissler","year":"2021","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1136\/ard.2006.065706","article-title":"Investigation of association between the TRAF family genes and RA susceptibility","volume":"66","author":"Potter","year":"2007","journal-title":"Ann. Rheum. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Xiang, Q., Chen, L., Hou, S., Fang, J., Zhou, Y., Bai, L., Liu, Y., Kijlstra, A., and Yang, P. (2014). TRAF5 and TRAF3IP2 gene polymorphisms are associated with Behcet\u2019s disease and Vogt-Koyanagi-Harada syndrome: A case-control study. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0084214"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.jcmg.2014.10.009","article-title":"Splenic metabolic activity predicts risk of future cardiovascular events: Demonstration of a cardiosplenic axis in humans","volume":"8","author":"Emami","year":"2015","journal-title":"JACC Cardiovasc. Imaging"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Lori, A., Perrotta, M., Lembo, G., and Carnevale, D. (2017). The Spleen: A Hub Connecting Nervous and Immune Systems in Cardiovascular and Metabolic Diseases. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18061216"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.diabres.2004.11.007","article-title":"Relationship of obesity and visceral adiposity with serum concentrations of CRP, TNF-alpha and IL-6","volume":"69","author":"Park","year":"2005","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1161\/CIRCRESAHA.108.177105","article-title":"Interferon-gamma, a Th1 cytokine, regulates fat inflammation: A role for adaptive immunity in obesity","volume":"103","author":"Rocha","year":"2008","journal-title":"Circ. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1016\/j.metabol.2012.01.018","article-title":"Systemic inflammation and insulin sensitivity in obese IFN-gamma knockout mice","volume":"61","author":"White","year":"2012","journal-title":"Metabolism"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1093\/cvr\/cvx197","article-title":"CD40L controls obesity-associated vascular inflammation, oxidative stress, and endothelial dysfunction in high fat diet-treated and db\/db mice","volume":"114","author":"Steven","year":"2018","journal-title":"Cardiovasc. Res."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Bae, H.R., Choi, M.S., Kim, S., Young, H.A., Gershwin, M.E., Jeon, S.M., and Kwon, E.Y. (2020). IFNgamma is a Key Link between Obesity and Th1-Mediated AutoImmune Diseases. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22010208"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1038\/s42255-021-00470-z","article-title":"Metabolic Messengers: Tumour necrosis factor","volume":"3","author":"Sethi","year":"2021","journal-title":"Nat. Metab."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/j.it.2023.06.002","article-title":"Physiological role of cytokines in the regulation of mammalian metabolism","volume":"44","author":"Trinh","year":"2023","journal-title":"Trends Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2629","DOI":"10.1002\/eji.200838893","article-title":"Obesity predisposes to Th17 bias","volume":"39","author":"Winer","year":"2009","journal-title":"Eur. J. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1016\/j.celrep.2015.07.014","article-title":"Obesity Drives Th17 Cell Differentiation by Inducing the Lipid Metabolic Kinase, ACC1","volume":"12","author":"Endo","year":"2015","journal-title":"Cell Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1146\/annurev-pathmechdis-051222-015350","article-title":"Immune Dysregulation in Obesity","volume":"20","author":"Jiang","year":"2025","journal-title":"Annu. Rev. Pathol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1038\/nm.2353","article-title":"B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies","volume":"17","author":"Winer","year":"2011","journal-title":"Nat. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1111\/j.1467-789X.2004.00144.x","article-title":"Obesity as a disease: No lightweight matter","volume":"5","author":"Conway","year":"2004","journal-title":"Obes. Rev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.bpg.2014.07.008","article-title":"Non-alcoholic fatty liver disease, obesity and the metabolic syndrome","volume":"28","author":"Dietrich","year":"2014","journal-title":"Best. Pract. Res. Clin. Gastroenterol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.phrs.2017.05.013","article-title":"Obesity and hypertension","volume":"122","author":"Seravalle","year":"2017","journal-title":"Pharmacol. Res."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Shiozawa, M., Kaneko, H., Itoh, H., Morita, K., Okada, A., Matsuoka, S., Kiriyama, H., Kamon, T., Fujiu, K., and Michihata, N. (2021). Association of Body Mass Index with Ischemic and Hemorrhagic Stroke. Nutrients, 13.","DOI":"10.3390\/nu13072343"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.atherosclerosis.2015.11.015","article-title":"Saturated fatty acids trigger TLR4-mediated inflammatory response","volume":"244","author":"Rocha","year":"2016","journal-title":"Atherosclerosis"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1146\/annurev-nutr-071816-064836","article-title":"Fatty Acids and NLRP3 Inflammasome-Mediated Inflammation in Metabolic Tissues","volume":"37","author":"Ralston","year":"2017","journal-title":"Annu. Rev. Nutr."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1002\/oby.21003","article-title":"Adipose tissue as an immunological organ","volume":"23","author":"Grant","year":"2015","journal-title":"Obesity"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Liu, R., and Nikolajczyk, B.S. (2019). Tissue Immune Cells Fuel Obesity-Associated Inflammation in Adipose Tissue and Beyond. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.01587"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/s41574-023-00908-2","article-title":"Macrophage and T cell networks in adipose tissue","volume":"20","author":"Jacks","year":"2024","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.cca.2012.12.007","article-title":"Role of leptin and adiponectin in insulin resistance","volume":"417","author":"Yadav","year":"2013","journal-title":"Clin. Chim. Acta"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1016\/j.cmet.2016.04.011","article-title":"Adiponectin, Leptin, and Fatty Acids in the Maintenance of Metabolic Homeostasis through Adipose Tissue Crosstalk","volume":"23","author":"Stern","year":"2016","journal-title":"Cell Metab."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1002\/j.2040-4603.2018.tb00036.x","article-title":"Adiponectin Regulation and Function","volume":"8","author":"Fang","year":"2018","journal-title":"Compr. Physiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1161\/HYPERTENSIONAHA.114.03575","article-title":"Endothelial dysfunction and hypertension","volume":"64","author":"Brandes","year":"2014","journal-title":"Hypertension"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1007\/5584_2016_90","article-title":"Endothelial Dysfunction and Hypertension","volume":"956","author":"Konukoglu","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Gutierrez-Cuevas, J., Santos, A., and Armendariz-Borunda, J. (2021). Pathophysiological Molecular Mechanisms of Obesity: A Link between MAFLD and NASH with Cardiovascular Diseases. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222111629"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Sandireddy, R., Sakthivel, S., Gupta, P., Behari, J., Tripathi, M., and Singh, B.K. (2024). Systemic impacts of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) on heart, muscle, and kidney related diseases. Front. Cell Dev. Biol., 12.","DOI":"10.3389\/fcell.2024.1433857"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1186\/s12933-024-02434-5","article-title":"Metabolic dysfunction-associated steatotic liver disease and cardiovascular risk: A comprehensive review","volume":"23","author":"Zheng","year":"2024","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/dom.14290","article-title":"Obesity as a multisystem disease: Trends in obesity rates and obesity-related complications","volume":"23","author":"Sarma","year":"2021","journal-title":"Diabetes Obes. Metab."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2218","DOI":"10.1093\/eurjpc\/zwac187","article-title":"Obesity and cardiovascular disease: Mechanistic insights and management strategies. A joint position paper by the World Heart Federation and World Obesity Federation","volume":"29","author":"Almahmeed","year":"2022","journal-title":"Eur. J. Prev. Cardiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/S0140-6736(22)01349-6","article-title":"Autoimmune diseases and cardiovascular risk: A population-based study on 19 autoimmune diseases and 12 cardiovascular diseases in 22 million individuals in the UK","volume":"400","author":"Conrad","year":"2022","journal-title":"Lancet"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1161\/ATVBAHA.107.140566","article-title":"TRAF-1, -2, -3, -5, and -6 are induced in atherosclerotic plaques and differentially mediate proinflammatory functions of CD40L in endothelial cells","volume":"27","author":"Zirlik","year":"2007","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Strohm, L., Ubbens, H., Munzel, T., Daiber, A., and Daub, S. (2022). Role of CD40(L)-TRAF signaling in inflammation and resolution-a double-edged sword. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.995061"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Zhang, S., Gang, X., Yang, S., Cui, M., Sun, L., Li, Z., and Wang, G. (2021). The Alterations in and the Role of the Th17\/Treg Balance in Metabolic Diseases. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.678355"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"7800","DOI":"10.4049\/jimmunol.181.11.7800","article-title":"TNF receptor-associated factor 5 is required for optimal T cell expansion and survival in response to infection","volume":"181","author":"Kraus","year":"2008","journal-title":"J. Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/S0092-8674(00)00078-7","article-title":"Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme","volume":"102","author":"Muramatsu","year":"2000","journal-title":"Cell"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1002\/eji.201848084","article-title":"B cell-intrinsic MyD88 signaling controls IFN-gamma-mediated early IgG2c class switching in mice in response to a particulate adjuvant","volume":"49","author":"Lee","year":"2019","journal-title":"Eur. J. Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.4049\/jimmunol.1900188","article-title":"TNF Receptor-Associated Factor 5 Limits Function of Plasmacytoid Dendritic Cells by Controlling IFN Regulatory Factor 5 Expression","volume":"203","author":"Kobayashi","year":"2019","journal-title":"J. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"145","DOI":"10.4049\/jimmunol.1301901","article-title":"TRAF5 negatively regulates TLR signaling in B lymphocytes","volume":"192","author":"Buchta","year":"2014","journal-title":"J. Immunol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1089\/ars.2009.2733","article-title":"Oxidized LDL: Diversity, patterns of recognition, and pathophysiology","volume":"13","author":"Levitan","year":"2010","journal-title":"Antioxid. Redox Signal"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1161\/CIRCRESAHA.110.223875","article-title":"Oxidation-specific epitopes are danger-associated molecular patterns recognized by pattern recognition receptors of innate immunity","volume":"108","author":"Miller","year":"2011","journal-title":"Circ. Res."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Rogero, M.M., and Calder, P.C. (2018). Obesity, Inflammation, Toll-Like Receptor 4 and Fatty Acids. Nutrients, 10.","DOI":"10.3390\/nu10040432"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/s41577-019-0215-7","article-title":"DAMP-sensing receptors in sterile inflammation and inflammatory diseases","volume":"20","author":"Gong","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/1074-7613(94)90095-7","article-title":"The immune responses in CD40-deficient mice: Impaired immunoglobulin class switching and germinal center formation","volume":"1","author":"Kawabe","year":"1994","journal-title":"Immunity"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/1074-7613(94)90073-6","article-title":"Mice deficient for the CD40 ligand","volume":"1","author":"Xu","year":"1994","journal-title":"Immunity"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1084\/jem.180.5.1889","article-title":"Humoral immune responses in CD40 ligand-deficient mice","volume":"180","author":"Renshaw","year":"1994","journal-title":"J. Exp. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1146\/annurev.immunol.14.1.591","article-title":"Immune regulation by CD40 and its ligand GP39","volume":"14","author":"Foy","year":"1996","journal-title":"Annu. Rev. Immunol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"3421","DOI":"10.4049\/jimmunol.1800337","article-title":"TRAF2 Deficiency in B Cells Impairs CD40-Induced Isotype Switching That Can Be Rescued by Restoring NF-kappaB1 Activation","volume":"201","author":"Woolaver","year":"2018","journal-title":"J. Immunol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/S1074-7613(00)80391-X","article-title":"Early lethality, functional NF-kappaB activation, and increased sensitivity to TNF-induced cell death in TRAF2-deficient mice","volume":"7","author":"Yeh","year":"1997","journal-title":"Immunity"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/S1074-7613(00)80113-2","article-title":"TRAF2 deficiency results in hyperactivity of certain TNFR1 signals and impairment of CD40-mediated responses","volume":"11","author":"Nguyen","year":"1999","journal-title":"Immunity"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Huang, L.Y., Chiu, C.J., Hsing, C.H., and Hsu, Y.H. (2022). Interferon Family Cytokines in Obesity and Insulin Sensitivity. Cells, 11.","DOI":"10.3390\/cells11244041"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.1126\/science.1118948","article-title":"Divergent immunoglobulin g subclass activity through selective Fc receptor binding","volume":"310","author":"Nimmerjahn","year":"2005","journal-title":"Science"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Vidarsson, G., Dekkers, G., and Rispens, T. (2014). IgG subclasses and allotypes: From structure to effector functions. Front. Immunol., 5.","DOI":"10.3389\/fimmu.2014.00520"},{"key":"ref_86","first-page":"224","article-title":"Correlation between cell aggregation and antibody production in IgE-producing plasma cells","volume":"10","author":"Hikosaka","year":"2017","journal-title":"Biochem. Biophys. Rep."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/bmt.2012.244","article-title":"Investigation of the freely available easy-to-use software \u2018EZR\u2019 for medical statistics","volume":"48","author":"Kanda","year":"2013","journal-title":"Bone Marrow Transplant."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/19\/9494\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T04:22:05Z","timestamp":1759292525000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/19\/9494"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,28]]},"references-count":87,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["ijms26199494"],"URL":"https:\/\/doi.org\/10.3390\/ijms26199494","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2025,9,28]]}}}