{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T16:54:19Z","timestamp":1784652859389,"version":"3.55.0"},"reference-count":154,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,7,24]],"date-time":"2022-07-24T00:00:00Z","timestamp":1658620800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Current Research Funds 2022, Ministry of Health, Italy"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Multiple sclerosis (MS) is an autoimmune neurodegenerative disorder of the central nervous system that presents heterogeneous clinical manifestations and course. It has been shown that different immune checkpoints, including Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4), can be involved in the pathogenesis of MS. CTLA-4 is a critical regulator of T-cell homeostasis and self-tolerance and represents a key inhibitor of autoimmunity. In this scopingreview, we resume the current preclinical and clinical studies investigating the role of CTLA-4 in MS with different approaches. While some of these studies assessed the expression levels of CTLA-4 on T cells by comparing MS patients with healthy controls, others focused on the evaluation of the effects of common MS therapies on CTLA-4 modulation or on the study of the CTLA-4 blockade or deficiency in experimental autoimmune encephalomyelitis models. Moreover, other studies in this field aimed to discover if the CTLA-4 gene might be involved in the predisposition to MS, whereas others evaluated the effects of treatment with CTLA4-Ig in MS. Although these results are of great interest, they are often conflicting. Therefore, further studies are needed to reveal the exact mechanisms underlying the action of a crucial immune checkpoint such as CTLA-4 in MS to identify novel immunotherapeutic strategies for MS patients.<\/jats:p>","DOI":"10.3390\/genes13081319","type":"journal-article","created":{"date-parts":[[2022,7,24]],"date-time":"2022-07-24T22:49:02Z","timestamp":1658702942000},"page":"1319","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["The Role of Cytotoxic T-Lymphocyte Antigen 4 in the Pathogenesis of Multiple Sclerosis"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4811-4694","authenticated-orcid":false,"given":"Maria Sofia","family":"Basile","sequence":"first","affiliation":[{"name":"IRCCS Centro Neurolesi \u201cBonino-Pulejo\u201d, Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Placido","family":"Bramanti","sequence":"additional","affiliation":[{"name":"IRCCS Centro Neurolesi \u201cBonino-Pulejo\u201d, Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela","family":"Mazzon","sequence":"additional","affiliation":[{"name":"IRCCS Centro Neurolesi \u201cBonino-Pulejo\u201d, Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,24]]},"reference":[{"key":"ref_1","first-page":"765","article-title":"Diagnosis and Treatment of Multiple Sclerosis A Review Clinical Review & Education JAMA|Review","volume":"325","author":"McGinley","year":"2021","journal-title":"Number"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.1177\/1352458520970841","article-title":"Rising prevalence of multiple sclerosis worldwide: Insights from the Atlas of MS, third edition","volume":"26","author":"Walton","year":"2020","journal-title":"Mult. 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