{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T19:30:07Z","timestamp":1786476607230,"version":"build-2736575974"},"reference-count":50,"publisher":"Wiley","issue":"41","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>In rheumatoid arthritis (RA), regulatory T cells (Tregs) within the synovium present a paradox: they are numerically enriched yet functionally impaired, leading to a loss of immune tolerance. Here, we report that synovial iron overload establishes a ferroptosis\u2010permissive microenvironment that disrupts Treg homeostasis. Exposure to RA synovial fluid induced ferroptosis, autoimmune Treg\u2010associated metabolic shifts through lipid peroxide\u2010driven mitochondrial dysfunction, characterized by electron transport chain (ETC) collapse and impaired oxidative phosphorylation. Mechanistically, metabolic disturbance by ferroptotic stress or complex III blockade triggered TXK kinase upregulation, which is required for the phosphorylation of STAT3 (Tyr705) and PLC\u03b31 (Tyr783), activating a proinflammatory transcriptional program that destabilized Treg identity and promoted Th17\u2010like conversion. Crucially, this pathogenic reprogramming was reversed through iron chelation or TXK inhibition in vitro and in vivo. Our findings unveil a ferroptosis\u2010ETC\u2010TXK\/STAT3 axis as a core mechanism of synovial Treg failure. Targeting synovial iron homeostasis or inhibiting TXK signaling thus represents a promising therapeutic strategy to restore immune tolerance in RA by rescuing Treg functionality.<\/jats:p>","DOI":"10.1002\/advs.202520519","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T14:27:13Z","timestamp":1779200833000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Disruption of Treg Homeostasis in Rheumatoid Arthritis via Ferroptosis\u2010Mediated ETC Collapse and TXK\u2010STAT3\/PLC\u03b31 Activation"],"prefix":"10.1002","volume":"13","author":[{"given":"Jingrong","family":"Chen","sequence":"first","affiliation":[{"name":"Division of Rheumatology Department of Medicine Songjiang Research Institute Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"Department of Immunology School of Cell and Gene Therapy Songjiang Research 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