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Here, we investigated consequences of insulin exposure for T cell function in the canonical autoimmunity of rheumatoid arthritis (RA). We observed that insulin levels correlated with the glycolytic index of CD4+ cells but suppressed transcription of insulin receptor substrates, which was inversely related to insulin sensitivity. This connection between insulin levels and the glycolytic index was not seen in CD4+ cells of healthy controls. Exposure of CD4+ cells to insulin induced a senescent state recognized by cell cycle arrest and DNA content enrichment measured by flow cytometry. It also resulted in accumulation of DNA damage marker \u03b3H2AX. Insulin suppressed IFN\u03b3 production and induced the senescence-associated secretome in CD4+ cell cultures and in patients with hyperinsulinemia. Inhibition of JAK-STAT signaling (JAKi) improved insulin signaling, which activated the glycolytic index and facilitated senescence in CD4+ cell cultures. Treatment with JAKi was associated with an abundance of na\u00efve and recent thymic emigrant T cells in the circulation of RA patients. Thus, we concluded that insulin exerts immunosuppressive ability by inducing senescence and inhibiting IFN\u03b3 production in CD4+ cells. JAKi promotes insulin effects and supports elimination of the pathogenic CD4+ cell in RA patients.<\/jats:p>","DOI":"10.3390\/cells13242124","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T05:58:27Z","timestamp":1734933507000},"page":"2124","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Insulin Sensitivity Controls Activity of Pathogenic CD4+ T Cells in Rheumatoid Arthritis"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1100-7577","authenticated-orcid":false,"given":"Malin C.","family":"Erlandsson","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Inflammation Research, Institute of Medicine, University of Gothenburg, 41346 Gothenburg, Sweden"},{"name":"Rheumatology Clinic, Sahlgrenska University Hospital, 41345 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Malmh\u00e4ll-Bah","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Inflammation Research, Institute of Medicine, University of Gothenburg, 41346 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venkataragavan","family":"Chandrasekaran","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Inflammation Research, Institute of Medicine, University of Gothenburg, 41346 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin M. 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Clin. Investig."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1172\/JCI88880","article-title":"Skeletal muscle inflammation and insulin resistance in obesity","volume":"127","author":"Wu","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.4049\/jimmunol.1800065","article-title":"Insulin Resistance in Macrophages Alters Their Metabolism and Promotes an M2-Like Phenotype","volume":"202","author":"Ieronymaki","year":"2019","journal-title":"J. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"441","DOI":"10.4093\/dmj.2022.0416","article-title":"Regulation of Cellular Senescence in Type 2 Diabetes Mellitus: From Mechanisms to Clinical Applications","volume":"47","author":"Iwasaki","year":"2023","journal-title":"Diabetes Metab. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1007\/s12032-013-0805-3","article-title":"Insulin receptor (IR) and insulin-like growth factor receptor 1 (IGF-1R) signaling systems: Novel treatment strategies for cancer","volume":"31","author":"Singh","year":"2014","journal-title":"Med. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1210\/js.2019-00065","article-title":"Hyperinsulinemia: An Early Indicator of Metabolic Dysfunction","volume":"3","author":"Thomas","year":"2019","journal-title":"J. Endocr. Soc."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"E2","DOI":"10.1152\/ajpendo.00441.2021","article-title":"Hyperinsulinemia: Beneficial or harmful or both on glucose homeostasis","volume":"323","author":"Xing","year":"2022","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2105","DOI":"10.1002\/art.23600","article-title":"Inflammation-associated insulin resistance: Differential effects in rheumatoid arthritis and systemic lupus erythematosus define potential mechanisms","volume":"58","author":"Chung","year":"2008","journal-title":"Arthritis Rheum."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2765","DOI":"10.1002\/art.22053","article-title":"Insulin resistance and impaired beta cell function in rheumatoid arthritis","volume":"54","author":"Dessein","year":"2006","journal-title":"Arthritis Rheum."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1002\/art.38986","article-title":"Insulin resistance in rheumatoid arthritis: Disease-related indicators and associations with the presence and progression of subclinical atherosclerosis","volume":"67","author":"Giles","year":"2015","journal-title":"Arthritis Rheumatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.4049\/jimmunol.1601011","article-title":"The Insulin Receptor Plays a Critical Role in T Cell Function and Adaptive Immunity","volume":"198","author":"Fischer","year":"2017","journal-title":"J. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1016\/j.cmet.2018.08.003","article-title":"Insulin Receptor-Mediated Stimulation Boosts T Cell Immunity during Inflammation and Infection","volume":"28","author":"Tsai","year":"2018","journal-title":"Cell Metab."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2158","DOI":"10.1016\/j.bbadis.2017.06.002","article-title":"IGF-1R signalling contributes to IL-6 production and T cell dependent inflammation in rheumatoid arthritis","volume":"1863","author":"Erlandsson","year":"2017","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1172\/JCI29069","article-title":"Inflammation and insulin resistance","volume":"116","author":"Shoelson","year":"2006","journal-title":"J. Clin. Investig."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e20191542","DOI":"10.1084\/jem.20191542","article-title":"T reg-specific insulin receptor deletion prevents diet-induced and age-associated metabolic syndrome","volume":"217","author":"Wu","year":"2020","journal-title":"J. Exp. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2569","DOI":"10.1002\/art.27584","article-title":"2010 Rheumatoid arthritis classification criteria: An American College of Rheumatology\/European League Against Rheumatism collaborative initiative","volume":"62","author":"Aletaha","year":"2010","journal-title":"Arthritis Rheum."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"101558","DOI":"10.1016\/j.molmet.2022.101558","article-title":"Chronic hyperinsulinemia promotes human hepatocyte senescence","volume":"64","author":"Baboota","year":"2022","journal-title":"Mol. Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nmeth.2089","article-title":"NIH Image to ImageJ: 25 years of image analysis","volume":"9","author":"Schneider","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Lyngfelt, L.I., Erlandsson, M.C., Nadali, M., Hedjazifar, S., Pullerits, R., Andersson, K.M., Brembeck, P., Silfversward, S.T., Smith, U., and Bokarewa, M.I. (2021). Impact of the Uncoupling Protein 1 on Cardiovascular Risk in Patients with Rheumatoid Arthritis. Cells, 10.","DOI":"10.3390\/cells10051131"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Nadali, M., Pullerits, R., Andersson, K.M.E., Silfversward, S.T., Erlandsson, M.C., and Bokarewa, M.I. (2017). High Expression of STAT3 in Subcutaneous Adipose Tissue Associates with Cardiovascular Risk in Women with Rheumatoid Arthritis. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18112410"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"536","DOI":"10.2119\/molmed.2015.00057","article-title":"Pathogenic Transdifferentiation of Th17 Cells Contribute to Perpetuation of Rheumatoid Arthritis during Anti-TNF Treatment","volume":"21","author":"Andersson","year":"2015","journal-title":"Mol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Love, M.I., Huber, W., and Anders, S. (2014). Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol., 15.","DOI":"10.1186\/s13059-014-0550-8"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.celrep.2019.08.068","article-title":"Restricting Glycolysis Preserves T Cell Effector Functions and Augments Checkpoint Therapy","volume":"29","author":"Renner","year":"2019","journal-title":"Cell Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2847","DOI":"10.1093\/bioinformatics\/btw313","article-title":"Complex heatmaps reveal patterns and correlations in multidimensional genomic data","volume":"32","author":"Gu","year":"2016","journal-title":"Bioinformatics"},{"key":"ref_26","unstructured":"Wei, T., and Simko, V. (2022, April 17). R Package \u2018Corrplot\u2019: Visualization of a Correlation Matrix. Available online: https:\/\/github.com\/taiyun\/corrplot."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1128\/MMBR.00031-10","article-title":"Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases","volume":"75","author":"Cargnello","year":"2011","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/s11357-020-00183-3","article-title":"Regulation of senescence traits by MAPKs","volume":"42","author":"Anerillas","year":"2020","journal-title":"Geroscience"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/s41392-021-00791-1","article-title":"The JAK\/STAT signaling pathway: From bench to clinic","volume":"6","author":"Hu","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.ebiom.2017.04.013","article-title":"Cellular Senescence: A Translational Perspective","volume":"21","author":"Kirkland","year":"2017","journal-title":"EBioMedicine"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1556","DOI":"10.1038\/s41591-022-01923-y","article-title":"Cellular senescence and senolytics: The path to the clinic","volume":"28","author":"Chaib","year":"2022","journal-title":"Nat. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"109202","DOI":"10.1016\/j.clim.2022.109202","article-title":"T-cell senescence: A crucial player in autoimmune diseases","volume":"248","author":"Lu","year":"2023","journal-title":"Clin. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1038\/nm.2130","article-title":"A CD8+ T cell transcription signature predicts prognosis in autoimmune disease","volume":"16","author":"McKinney","year":"2010","journal-title":"Nat. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"eabd7600","DOI":"10.1126\/sciadv.abd7600","article-title":"Gene expression signatures of target tissues in type 1 diabetes, lupus erythematosus, multiple sclerosis, and rheumatoid arthritis","volume":"7","author":"Szymczak","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1186\/s13075-015-0564-y","article-title":"Effect of prednisone on type I interferon signature in rheumatoid arthritis: Consequences for response prediction to rituximab","volume":"17","author":"Vosslamber","year":"2015","journal-title":"Arthritis Res. Ther."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1136\/ard.2006.063412","article-title":"Rheumatoid arthritis subtypes identified by genomic profiling of peripheral blood cells: Assignment of a type I interferon signature in a subpopulation of patients","volume":"66","author":"Wijbrandts","year":"2007","journal-title":"Ann. Rheum. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"641","DOI":"10.2337\/diab.38.5.641","article-title":"Effect of interferon on glucose tolerance and insulin sensitivity","volume":"38","author":"Koivisto","year":"1989","journal-title":"Diabetes"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.immuni.2018.05.005","article-title":"Virus-Induced Interferon-gamma Causes Insulin Resistance in Skeletal Muscle and Derails Glycemic Control in Obesity","volume":"49","author":"Sestan","year":"2018","journal-title":"Immunity"},{"key":"ref_39","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_40","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1136\/annrheumdis-2021-221840","article-title":"Hypoglycaemia following JAK inhibitor treatment in patients with diabetes","volume":"81","author":"Tas","year":"2022","journal-title":"Ann. Rheum. Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"117045","DOI":"10.1016\/j.lfs.2019.117045","article-title":"Inhibition of JAK-STAT and NF-kappaB signalling systems could be a novel therapeutic target against insulin resistance and type 2 diabetes","volume":"239","author":"Bako","year":"2019","journal-title":"Life Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1097\/EDE.0000000000000891","article-title":"Use of Dipeptidyl Peptidase-4 Inhibitors and New-onset Rheumatoid Arthritis in Patients with Type 2 Diabetes","volume":"29","author":"Douros","year":"2018","journal-title":"Epidemiology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1968","DOI":"10.1136\/annrheumdis-2014-205216","article-title":"Dipeptidyl peptidase-4 inhibitors in type 2 diabetes may reduce the risk of autoimmune diseases: A population-based cohort study","volume":"74","author":"Kim","year":"2015","journal-title":"Ann. Rheum. Dis."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Su, Y.J., Huang, J.Y., Chu, C.Q., and Wei, J.C. (2022). Sulfonylureas or biguanides is associated with a lower risk of rheumatoid arthritis in patients with diabetes: A nationwide cohort study. Front. Med., 9.","DOI":"10.3389\/fmed.2022.934184"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1007\/s10654-023-01000-9","article-title":"Repurposing antidiabetic drugs for rheumatoid arthritis: Results from a two-sample Mendelian randomization study","volume":"38","author":"Qin","year":"2023","journal-title":"Eur. J. 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