{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T03:52:09Z","timestamp":1782877929422,"version":"3.54.5"},"reference-count":39,"publisher":"American Society for Clinical Investigation","issue":"13","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":50,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Natural Science Foundation of China General Fund Project","award":["82370521"],"award-info":[{"award-number":["82370521"]}]},{"name":"the National Natural Science Foundation of China General Fund Project","award":["32370962"],"award-info":[{"award-number":["32370962"]}]},{"name":"National Natural Science Foundation of China Youth Science Fund Project","award":["82102687"],"award-info":[{"award-number":["82102687"]}]},{"name":"National Natural Science Foundation of China Youth Science Fund Project","award":["81902470"],"award-info":[{"award-number":["81902470"]}]},{"name":"National Natural Science Foundation of China Youth Science Fund Project","award":["82201922"],"award-info":[{"award-number":["82201922"]}]},{"name":"the Innovation of Science and Technology, Fujian Province","award":["No.2023Y9054"],"award-info":[{"award-number":["No.2023Y9054"]}]},{"name":"Regional joint key support project of National Natural Science Foundation of China","award":["U23A20428"],"award-info":[{"award-number":["U23A20428"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,1]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>Immune checkpoint inhibitor\u2013induced inflammatory arthritis (ICI-IA) significantly impairs cancer therapy and patient quality of life, yet its pathogenic mechanisms remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Through integrated single-cell multi-omics analysis of paired peripheral blood, synovial fluid, and tumor samples from longitudinal ICI-IA cohorts and matched controls, we identified a unique regulatory T-cell (Treg) population coexpressing CD137 and IL-6R (AtpTreg).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>These cells exhibited reduced immunosuppressive capacity while aberrantly producing high levels of IL-17 and promoting proinflammatory responses of synoviocytes. AtpTreg exhibits shared clonotypes and phenotypes across tissue compartments. Notably, AtpTreg frequency correlates with increased arthritis severity yet paradoxically associates with improved overall survival. Anti-IL6R therapy reduced AtpTreg levels, corresponding with improved arthritis outcomes and quality of life, without compromising anti-tumor immunity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Our findings define a pathogenic Treg subset in ICI-IA and validate IL-6R blockade as a mechanism-based therapeutic strategy, bridging mechanistic discovery to clinical translation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>TRIAL REGISTRATION<\/jats:title>\n                    <jats:p>NCT07357636.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>FUNDING<\/jats:title>\n                    <jats:p>The National Natural Science Foundation of China General Fund Project; National Natural Science Foundation of China Youth Science Fund Project; Regional joint key support project of National Natural Science Foundation of China; Natural Science Foundation of Fujian Province; Joint Funds for the Innovation of Science and Technology, Fujian Province.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1172\/jci200135","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T16:00:31Z","timestamp":1778601631000},"source":"Crossref","is-referenced-by-count":1,"title":["IL-6 receptor blockade impedes proinflammatory atypical Treg subset associated with immune checkpoint inhibitor\u2013induced inflammatory arthritis"],"prefix":"10.1172","volume":"136","author":[{"given":"Yifei","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China."},{"name":"Institute of Abdominal Surgery, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China."},{"name":"Fujian Provincial Key Laboratory of Precision Medicine for Cancer, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China."},{"name":"Department of Hepatobiliary and Pancreatic Surgery, National Regional Medical Center Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nianqi","family":"Liu","sequence":"additional","affiliation":[{"name":"Faculty of Psychology, Institute of Educational Science, Huazhong University of Science and Technology, Wuhan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China."},{"name":"State Key Laboratory of Oncology in South China, Guangdong Key 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