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Among its many manifestations, lupus nephritis (LN) stands out as one of the most severe and life-threatening complications, affecting up to 60% of SLE patients. LN primarily results from a type III hypersensitivity reaction in which immune complexes are deposited within the kidney. This leads to progressive glomerular and tubulointerstitial lesions compromising renal function. A significant portion of patients presenting with LN will progress to end-stage renal disease (ERSD). Despite advances in treatment strategies, including standard and targeted biologic immunosuppressants, many patients with LN fail to achieve long-term remission, leaving a significant need for safer and more effective therapies. In recent years, T-cell-based therapies have emerged as a promising frontier in the treatment of a variety of conditions including autoimmune diseases. Specifically, chimeric antigen receptor (CAR) T-cell therapies aimed at depleting antibody-producing B cells have demonstrated the ability to restore immune tolerance in several preclinical models of diseases with B-cell-driven pathologies, including SLE. In the case of LN, CAR T-cell therapies have also been deployed in clinical trials to treat patients with refractory disease. The positive results of initial clinical trials provide strong evidence that B-cell-targeted cellular therapies such as CAR T cells targeting B-cell markers CD19 and B-cell maturation antigen (BCMA) might be an effective modality for rebalancing the immune system through the elimination of autoreactive B cells. This review examines the current state of CAR T-cell therapies and their applications in LN by exploring the mechanisms, challenges, and the potential of this unique treatment approach.<\/jats:p>","DOI":"10.1177\/09636897251371114","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T08:31:08Z","timestamp":1761899468000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Harnessing T-cell therapy for lupus nephritis: Opportunities and challenges"],"prefix":"10.1177","volume":"34","author":[{"given":"Megan","family":"Tennant","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Immunology, Medical University of South Carolina, Charleston, SC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa","family":"Cunningham","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, Medical University of South Carolina, Charleston, SC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9734-2343","authenticated-orcid":false,"given":"Richard","family":"ONeil","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Immunology, Medical University of South Carolina, Charleston, SC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2025,10,31]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-122-12-199506150-00009"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.42375"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2016.03.042"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfs073"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00475"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semnephrol.2015.08.006"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2015.159"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1191\/0961203305lu2055oa"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1159\/000081551"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2022.2072143"},{"issue":"189","key":"e_1_3_3_12_2","first-page":"1","article-title":"Systemic lupus with nephritis: a long-term study","volume":"48","author":"Cameron JS","year":"1979","unstructured":"Cameron JS, et al. 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