{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T20:55:55Z","timestamp":1789678555536,"version":"4.0.1"},"reference-count":51,"publisher":"American Society for Clinical Investigation","issue":"21","license":[{"start":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:00:00Z","timestamp":1762128000000},"content-version":"vor","delay-in-days":62,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82272192,82074538,82001550"],"award-info":[{"award-number":["82272192,82074538,82001550"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100012247","name":"Program of Shanghai Academic Research Leader","doi-asserted-by":"crossref","award":["22XD1420400"],"award-info":[{"award-number":["22XD1420400"]}],"id":[{"id":"10.13039\/501100012247","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Shanghai \u201cYiyuan New Star\u201d Outstanding Youth Medical Talent Program","award":["20244Z0012"],"award-info":[{"award-number":["20244Z0012"]}]},{"name":"the Shanghai Municipal 2021 \u201cScience and Technology Innovation Action Plan\u201d","award":["21S31902600"],"award-info":[{"award-number":["21S31902600"]}]},{"name":"Innovative Research Team of High-level Local Universities in Shanghai, Shanghai Key Laboratory for Acupuncture Mechanism and Acupoint Function","award":["21DZ2271800"],"award-info":[{"award-number":["21DZ2271800"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,3]]},"abstract":"<jats:p>\n                    Sepsis is a life-threatening disease caused by a dysfunctional host response to infection. During sepsis, inflammation-related immunosuppression is the critical factor causing secondary infection and multiple organ dysfunction syndrome. The regulatory mechanisms underlying Treg differentiation and function, which significantly contribute to septic immunosuppression, require further clarification. In this study, we found that neutrophil extracellular traps (NETs) participated in the development of sepsis-induced immunosuppression by enhancing Treg differentiation and function via direct interaction with CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Briefly, NETs anchored enolase 1 (ENO1) on the membrane of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells through its key protein myeloperoxidase (MPO) and subsequently recruited interferon-induced transmembrane protein 2 (IFITM2). IFITM2 acted as a DNA receptor that sensed NET-DNA and activated intracellular RAS-associated protein 1B (RAP1B) and its downstream ERK signaling pathway to promote Treg differentiation and function. ENO1 inhibition significantly attenuated NET-induced Treg differentiation and alleviated sepsis in mice. Overall, we demonstrated the role of NETs in sepsis-induced immunosuppression by enhancing Treg differentiation, identified ENO1 as an anchor of NET-MPO, and elucidated the downstream molecular mechanism by which IFITM2-RAP1B-ERK regulates Treg differentiation. These findings improve our understanding of the immunopathogenesis of sepsis and provide potential therapeutic targets for sepsis-induced immunosuppression.\n                  <\/jats:p>","DOI":"10.1172\/jci183541","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T16:00:59Z","timestamp":1756828859000},"source":"Crossref","is-referenced-by-count":14,"title":["Myeloperoxidase-anchored ENO1 mediates neutrophil extracellular trap DNA to enhance Treg differentiation via IFITM2 during sepsis"],"prefix":"10.1172","volume":"135","author":[{"given":"Yi","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, China."},{"name":"Shanghai Key Laboratory of Perioperative Stress and Protection, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenjia","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, China."},{"name":"Shanghai Key Laboratory of Perioperative Stress and Protection, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiya","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, China."},{"name":"Shanghai Key Laboratory of Perioperative Stress and Protection, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, China."},{"name":"Shanghai Key Laboratory of Perioperative Stress and Protection, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, China."},{"name":"Shanghai Key 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