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Dysfunctional SOCS proteins in immune and tissue\u2010resident cells may contribute to chronic inflammation. Abnormal expression of SOCS proteins, including SOCS1, SOCS2, SOCS3, SOCS5, SOCS6, and SOCS7, has been reported in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), playing a vital role in disease pathogenesis. The expression of SOCS1 and SOCS3 varies across different cell types and stages of the disease. Genetic polymorphisms, epigenetic modifications, microRNAs, cytokines, hormones, therapeutic agents, and gender factors can influence SOCS1 and SOCS3 expression in MS patients and EAE mice. The functional impact of SOCS1 and SOCS3 is cell\u2010type specific, with distinct roles in T cell subsets, microglia\/macrophages, dendritic cells, astrocytes, and oligodendrocytes. In particular, SOCS1 and SOCS3 affect T cell subset differentiation, Th17\/Treg cell balance, microglial\/macrophage polarization, dendritic cell functions, as well as oligodendrocyte survival and activity. Therapeutic approaches targeting SOCS molecules, including SOCS1 mimetic peptides, have demonstrated promise in EAE models. This review provides a comprehensive explanation regarding the expression patterns of SOCS molecules in MS patients and EAE model, factors affecting their expression and their mechanistic role in disease immunopathogenesis, as well as highlights their potential as a therapeutic target for MS.<\/jats:p>","DOI":"10.1111\/sji.70113","type":"journal-article","created":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T04:25:52Z","timestamp":1777695952000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Abnormal Expression of Suppressor of Cytokine Signalling (\n                    <scp>SOCS<\/scp>\n                    ) Molecules Contributes to the Development of Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis"],"prefix":"10.1111","volume":"103","author":[{"given":"Abdollah","family":"Jafarzadeh","sequence":"first","affiliation":[{"name":"Department of Immunology, School of Medicine Kerman University of Medical Sciences  Kerman Iran"},{"name":"Applied Cellular and Molecular Research Center Kerman University of Medical Sciences  Kerman Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Narges","family":"Mikaeili","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Medicine Rafsanjan University of Medical Sciences  Rafsanjan Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zahra","family":"Jafarzadeh","sequence":"additional","affiliation":[{"name":"Student Research Committee, School of Medicine Kerman University of Medical Sciences  Kerman Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,5,1]]},"reference":[{"key":"e_1_2_16_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000037297"},{"key":"e_1_2_16_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.compbiomed.2022.105856"},{"key":"e_1_2_16_4_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a028977"},{"key":"e_1_2_16_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2021.109443"},{"key":"e_1_2_16_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241612699"},{"key":"e_1_2_16_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/sclerosis2030009"},{"key":"e_1_2_16_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2023.1101379"},{"key":"e_1_2_16_9_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20190460"},{"key":"e_1_2_16_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms252010931"},{"key":"e_1_2_16_11_1","doi-asserted-by":"publisher","DOI":"10.5001\/omj.2016.08"},{"key":"e_1_2_16_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-014-0443-z"},{"key":"e_1_2_16_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00791-1"},{"key":"e_1_2_16_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/cea.14385"},{"issue":"174","key":"e_1_2_16_15_1","article-title":"Aberrant Expression of SOCS Impairs the Anti\u2010Leishmanial Immune Response","volume":"7","author":"Jafarzadeh A.","year":"2023","journal-title":"Cytokine"},{"key":"e_1_2_16_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-017-0177-y"},{"key":"e_1_2_16_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.727987"},{"key":"e_1_2_16_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2024.155558"},{"key":"e_1_2_16_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/hel.13105"},{"key":"e_1_2_16_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.970508"},{"key":"e_1_2_16_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2014.09.011"},{"key":"e_1_2_16_22_1","doi-asserted-by":"publisher","DOI":"10.32598\/bcn.9.6.458"},{"key":"e_1_2_16_23_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.110.207464"},{"key":"e_1_2_16_24_1","first-page":"1","article-title":"SOCS Proteins in Development and Disease","volume":"2","author":"Trengove M. 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