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This article provides a systematic review of the developmental trajectory and core concepts of CAR-T-cell therapy in autoimmune diseases, emphasizing its conceptual evolution from traditional \u201ckilling\u201d strategies to \u201cprecision immune remodeling\u201d. Leveraging multitarget approaches (e.g., CD19 and B-cell maturation antigen) and chimeric autoantigen receptor technology, it achieves efficient elimination of pathogenic B cells, plasma cells, and autoreactive T cells, along with profound remodeling of the immune microenvironment, thereby inducing long-term disease remission and restoring immune tolerance. Nevertheless, unresolved challenges still exist in monotherapy strategies, such as antigen escape, nontumor toxicity of emerging targets, limited in\u00a0vivo persistence, high production costs, and immune reconstitution imbalance. Future research ought to concentrate on the development of multitarget\/logic-gated chimeric antigen receptor constructs, the optimization of chimeric antigen receptor architecture and nonviral delivery systems, the validation of the long-term safety of universal CAR-T cells, the customization of personalized treatment regimens, and the exploration of mechanisms for modulating the immune microenvironment. This review emphasizes that CAR-T-cell therapy shows potential for initiating a new era of personalized, mechanism-driven treatment for autoimmune diseases, offering crucial insights for clinical translation.<\/jats:p>","DOI":"10.34133\/research.1239","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T08:35:09Z","timestamp":1773822909000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":0,"title":["Chimeric Antigen Receptor T-Cell Revolution Remodeling Immunity to Conquer Autoimmune Disease"],"prefix":"10.34133","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2041-5743","authenticated-orcid":false,"given":"Wenxia","family":"Shao","sequence":"first","affiliation":[{"name":"Affiliated Hangzhou First People\u2019s Hospital, School of Medicine, \rWestlake University, Hangzhou 310006, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiayu","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Medical Technology and Information Engineering, \rZhejiang Chinese Medical University, Hangzhou 310053, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Oncology, Suzhou Cancer Center Core Laboratory, \rThe Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou 215001, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daojun","family":"Yu","sequence":"additional","affiliation":[{"name":"Affiliated Hangzhou First People\u2019s Hospital, School of Medicine, \rWestlake University, Hangzhou 310006, China."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"221","published-online":{"date-parts":[[2026,5,18]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.06.027"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-024-01139-z"},{"issue":"7","key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1038\/d41573-025-00085-z","article-title":"The race to reset autoimmune diseases","volume":"24","author":"Bhandari M","year":"2025","unstructured":"Bhandari M, Smith JF, Capra E, Yang G. 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