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Its unique efficacy in refractory AIDs relies on depleting autoreactive B cells and driving antigen\u2010na\u00efve immune reconstitution, achieving durable drug\u2010free remission in early\u2010phase trials. Despite promising clinical and serological responses lasting 2\u20135 years without long\u2010term immunosuppression, the field faces unmet needs: complex manufacturing, limited tissue penetration, antigen escape, immunological sequelae, and lack of predictive biomarkers. Existing reviews predominantly focus on oncology adaptations or isolated technical aspects, lacking systematic integration of mechanisms, challenges, and precision\u2010oriented innovations for rheumatic diseases. This review comprehensively summarizes CAR\u2010T's action mechanisms in AIDs, analyzes core clinical challenges, and highlights emerging strategies\u2014including universal\/in vivo\u2010generated CAR\u2010T cells, multitargeted\/logic\u2010gated designs, organ\u2010homing engineering, and rational combinations with tolerance\u2010enhancing agents. It further emphasizes multiomics integration (single\u2010cell transcriptomics, spatial mapping, B\u2010cell receptor\/T\u2010cell receptor repertoire analysis) for patient stratification and relapse prediction. By bridging mechanism\u2010driven engineering with clinical translation, this work provides an actionable framework to advance CAR\u2010T toward functional immune reset, enabling precision immunotherapy for refractory rheumatic diseases and AIDs.<\/jats:p>","DOI":"10.1002\/mco2.70658","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T14:26:29Z","timestamp":1773757589000},"source":"Crossref","is-referenced-by-count":3,"title":["Application and Challenges of Chimeric Antigen Receptor T Cell Therapy in Systemic Rheumatic Diseases and Autoimmune Disorders"],"prefix":"10.1002","volume":"7","author":[{"given":"Zhidan","family":"Fan","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology Children's Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Children's 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