{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T12:50:47Z","timestamp":1787921447318,"version":"build-2784847793"},"reference-count":50,"publisher":"American Society for Clinical Investigation","issue":"6","license":[{"start":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T00:00:00Z","timestamp":1742774400000},"content-version":"vor","delay-in-days":48,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Science Foundation of Jiangsu Higher Education Institution-Key Program","award":["21KJA310002"],"award-info":[{"award-number":["21KJA310002"]}]},{"name":"Soochow University Research Development Funds","award":["Q424900220"],"award-info":[{"award-number":["Q424900220"]}]},{"name":"Soochow University Interdisciplinary Medicine Program Funds","award":["50340000122"],"award-info":[{"award-number":["50340000122"]}]},{"name":"Suzhou Key Program Special Funds in XJTLU","award":["KSF-A-21"],"award-info":[{"award-number":["KSF-A-21"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["31470840"],"award-info":[{"award-number":["31470840"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,24]]},"abstract":"<jats:p>\n                    Induction of podoplanin (PDPN) expression is a critical response of macrophages to LPS stimulation or bacterial infection in sepsis, but how this key process of TLR4-stimulated PDPN upregulation is regulated and the effect of PDPN expression on macrophage function remain elusive. Here, we determined how this process is regulated in vitro and in vivo. PDPN failed to be upregulated in TLR4-stimulated macrophages deficient in adhesion and degranulation-promoting adapter protein (ADAP), which could be rescued by the reconstitution of ADAP. A distinct PDPN\n                    <jats:sup>hi<\/jats:sup>\n                    peritoneal macrophage (PM) subset, which exhibited an M2-like phenotype and enhanced phagocytic activity, was generated in WT but not in ADAP-deficient septic mice. The blockade of PDPN\n                    <jats:sup>hi<\/jats:sup>\n                    PMs mimicked the effect of ADAP deficiency, which exacerbated sepsis. Mechanistically, Bruton\u2019s tyrosine kinase\u2013mediated (BTK-mediated) tyrosine phosphorylation of ADAP at Y\n                    <jats:sup>571<\/jats:sup>\n                    worked together with mTOR to converge on STAT3 activation for the transactivation of the PDPN promoter. Moreover, agonist activation of STAT3 profoundly potentiated the PDPN\n                    <jats:sup>hi<\/jats:sup>\n                    PM subset generation and alleviated sepsis severity in mice. Together, our findings reveal a mechanism whereby ADAP resets macrophage function by controlling the TLR4-induced upregulation of PDPN as a host innate immune defense during sepsis.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.186456","type":"journal-article","created":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T12:01:02Z","timestamp":1738670462000},"source":"Crossref","is-referenced-by-count":13,"title":["Molecular control of PDPNhi macrophage subset induction by ADAP as a host defense in sepsis"],"prefix":"10.1172","volume":"10","author":[{"given":"Pengchao","family":"Zhang","sequence":"first","affiliation":[{"name":"MOE Key Laboratory of Geriatric Diseases and Immunology, Institutes of Biology and Medical Sciences, Suzhou Medical College of Soochow University, Soochow University, Suzhou, Jiangsu Province, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinning","family":"Wang","sequence":"additional","affiliation":[{"name":"MOE Key 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