《生命科学》 2026, 38(4): 635-644

风湿免疫病的细胞治疗进展

尹张奕¹ , 魏莹莹^2,3,* , 钟继新^2,3,4,*

¹华中科技大学同济医学院，第二临床学院，武汉 430030 ²福建医科大学附属协和医院风湿内科，福州 350001 ³福建省临床免疫研究所，福州 350001 ⁴华中科技大学同济医学院附属同济医院，血管衰老教育部重点实验室，武汉 430030

摘　要：

风湿免疫病是一组以自身免疫异常为核心的慢性疾病，传统药物治疗存在全身性副作用及难以实现免疫学缓解等局限。近年来，细胞治疗展现出突破性潜力。CAR-T疗法通过靶向B细胞表面抗原（如CD19、BCMA等）实现快速持久的B细胞耗竭，在系统性红斑狼疮、类风湿关节炎等难治性疾病中取得显著临床缓解。在干细胞疗法中，间充质干细胞（MSCs）和造血干细胞移植（HSCT）通过免疫调节与组织修复功能，在多种风湿免疫病中改善炎症微环境，实现长期缓解。尽管细胞治疗仍面临靶点选择、长期安全性及高成本等挑战，基因编辑、联合治疗及个体化方案优化等策略有望推动细胞治疗进展，实现风湿免疫病的深度缓解乃至治愈。本文系统综述了CAR-T细胞疗法与干细胞疗法在风湿免疫病治疗中的最新进展。

通讯作者：魏莹莹 , Email:824237042@qq.com 钟继新 , Email:zhongjixin620@163.com

Advances in cell-based therapy for rheumatic immune diseases

YIN Zhang-Yi¹ , WEI Ying-Ying^2,3,* , ZHONG Ji-Xin^2,3,4,*

¹Second Clinical College, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China ²Department of Rheumatology, Union Hospital, Fujian Medical University, Fuzhou 350001 ³Fujian Institute of Clinical Immunology, Fuzhou, 350001, China ⁴Key Laboratory of Vascular Aging (HUST), Ministry of Education, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China

Abstract:

Rheumatic immune diseases are chronic disorders driven by autoimmune dysregulation. Conventional pharmacotherapies, including nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, and disease-modifying antirheumatic drugs (DMARDs), have significant limitations such as systemic toxicity, infection risk, and failure to achieve sustained immunological remission. Cell-based therapies have recently emerged as groundbreaking strategies with the potential to reset immune tolerance and induce deep remission. This review systematically advances the understanding of two major cellular approaches: chimeric antigen receptor (CAR)-T cell therapy and stem cell therapy. CAR-T therapy targeting B cell surface antigens, particularly CD19 and BCMA, induces rapid and profound B-cell depletion, leading to remarkable clinical responses in refractory systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), immune-mediated necrotizing myopathy (IMNM), and systemic sclerosis (SSc). Emerging innovations, including logic-gated CAR-T, RNA-engineered CAR-T (rCAR-T), allogeneic CRISPR-edited CAR-T, and CAR-natural killer (NK) cells, are enhancing safety, scalability, and accessibility. Fourth-generation CAR-T cells engineered to secrete anti-inflammatory cytokines (e.g., anti-IL-6, anti-TNFα) have shown feasibility in early-phase trials for RA. Parallel advancements in stem cell therapy demonstrate that mesenchymal stem cells (MSCs) modulate inflammatory microenvironments through paracrine signaling and cell-cell contact, improving outcomes in SLE, RA, multiple sclerosis (MS), and Sjögren′s syndrome (SS). Hematopoietic stem cell transplantation (HSCT) offers long-term, drug-free remission in severe refractory cases by resetting the immune system, with established efficacy in SSc and MS. Despite these breakthroughs, challenges including optimal target selection, long-term safety (e.g., infection risk), high costs, and manufacturing complexities remain. Future directions involve gene editing (CRISPR/Cas9), combination regimens, and personalized protocols to translate these therapies from bench to bedside. Collectively, cell-based therapies hold the potential to achieve deep remission or even functional cure for rheumatic immune diseases.

Communication Author：WEI Ying-Ying , Email:824237042@qq.com ZHONG Ji-Xin , Email:zhongjixin620@163.com