{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T06:07:14Z","timestamp":1784786834990,"version":"3.55.0"},"reference-count":96,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is a key immune checkpoint involved in immune regulation. CTLA-4 inhibitors have been widely used in cancer therapy and have attracted increasing attention in autoimmune diseases such as Sj\u00f6gren\u2019s syndrome (SS) in recent years. CTLA-4 modulates multiple immune processes, including genetic susceptibility, immune cell subsets, and inflammatory cytokine levels. CTLA-4, together with co-inhibitory receptors including Programmed cell death protein 1 (PD-1), T cell immunoreceptor with Ig and ITIM domains (TIGIT) and T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), forms a multi-layered immunosuppressive network. It modulates the balance of T cell subsets, regulates B cell receptor (BCR)-related pathways and downstream molecules such as Bruton\u2019s tyrosine kinase (BTK), and thereby orchestrates cellular and humoral immunity. CTLA-4 inhibitors used in cancer immunotherapy may trigger immune-related adverse events resembling Sj\u00f6gren\u2019s syndrome. Abatacept, a CTLA-4-Ig fusion protein that blocks T-cell costimulation, has been investigated as a therapeutic candidate for primary Sj\u00f6gren\u2019s syndrome (pSS). Open-label clinical studies consistently indicate that abatacept reduces disease activity, improves salivary gland function, and alleviates systemic symptoms. However, findings from randomized controlled trials remain inconsistent: some show no significant clinical benefit compared with placebo, whereas others demonstrate improvements in clinical indices, patient-reported outcomes, and laboratory parameters. Currently, the precise mechanism of CTLA-4 in the pathogenesis of Sj\u00f6gren\u2019s syndrome\\ remains incompletely clarified, and high-quality evidence supporting CTLA-4-targeted therapy is still limited. Further research is needed to validate the therapeutic value and optimal application of abatacept and other CTLA-4-modulating agents in Sj\u00f6gren\u2019s syndrome.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1868113","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T05:41:15Z","timestamp":1784785275000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The role and function of CTLA-4 in Sj\u00f6gren\u2019s syndrome"],"prefix":"10.3389","volume":"17","author":[{"given":"Ji","family":"Wen","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology, West China Hospital, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingshu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, West China Hospital, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linshen","family":"Xie","sequence":"additional","affiliation":[{"name":"Poisoning Department\/Nephrology Department, West China Fourth Hospital Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dingzi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Occupational Health and Occupational Medicine Key Laboratory of Sichuan Provincial Health Commission, West China School of Public Health and West China Fourth Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menglin","family":"Chen","sequence":"additional","affiliation":[{"name":"Poisoning Department\/Nephrology Department, West China Fourth Hospital Sichuan University","place":["Chengdu, Sichuan, 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