{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T08:01:26Z","timestamp":1781164886040,"version":"3.54.1"},"reference-count":50,"publisher":"American Association for the Advancement of Science (AAAS)","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82371815, 82373463, 8207343"],"award-info":[{"award-number":["82371815, 82373463, 8207343"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["spj.science.org"],"crossmark-restriction":true},"short-container-title":["Biomater Res"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by aberrant T cell activity and excessive autoantibody production. Follicular helper T cells (Tfh) play a pivotal role in promoting B cell-mediated autoantibody generation, contributing to SLE progression. Although mesenchymal stem cell-derived exosomes (MSC-Exos) exhibit immunomodulatory properties, their effects on Tfh in SLE and the underlying mechanisms remain unclear. To address this, we first analyzed sorted Tfh from an imiquimod-induced lupus murine model (IMQ-SLE) and found that MSC-Exos effectively suppressed Tfh function. Consistently, Tfh polarization assays demonstrated that MSC-Exos modulate Tfh differentiation in\u00a0vitro. Subsequently, we evaluated the therapeutic potential of intravenous MSC-Exos administration and confirmed that MSC-Exos markedly inhibited Tfh expansion and function in\u00a0vivo. Further RNA sequencing followed by validation experiments identified that MSC-Exos restore calcium homeostasis in Tfh. Mechanically, MSC-Exos down-regulate stromal interaction molecule 1 (Stim1) and Orai1 expression, inhibiting nuclear factor of activated T cells (NFAT) and nuclear factor \u03baB (NF-\u03baB) activation. In parallel, MSC-Exos mitigate calcium overload-induced mitochondrial damage by suppressing mitochondrial calcium uniporter (MCU) expression. Finally, we observed that MSC-Exos also promote the differentiation of follicular regulatory T cells (Tfr) both in\u00a0vivo and in\u00a0vitro. These findings suggest that MSC-Exos ameliorate SLE by correcting cellular calcium dysregulation and mitochondrial damage in Tfh while simultaneously restoring the Tfh\/Tfr imbalance, highlighting their potential as a therapeutic strategy for SLE.<\/jats:p>","DOI":"10.34133\/bmr.0255","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T23:13:54Z","timestamp":1756422834000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":3,"title":["Mesenchymal Stem Cell-Derived Exosomes Inhibit Stim1\u2013Orai1 Signaling and Calcium Overload-Induced Mitochondrial Damage of Follicular Helper T Cells in Lupus"],"prefix":"10.34133","volume":"29","author":[{"given":"Yingyu","family":"Wang","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Huashan Hospital, \rFudan University, Shanghai, China."},{"name":"Institute of Rheumatology, Immunology and Allergy, \rFudan University, Shanghai, 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