{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T23:07:20Z","timestamp":1791500840741,"version":"4.3.4"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2022,9,8]],"date-time":"2022-09-08T00:00:00Z","timestamp":1662595200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"},{"start":{"date-parts":[[2022,9,8]],"date-time":"2022-09-08T00:00:00Z","timestamp":1662595200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2022,9,8]],"date-time":"2022-09-08T00:00:00Z","timestamp":1662595200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,11,25]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Dectin-1 is known to drive proinflammatory cytokine production by macrophages and dendritic cells which promotes Th17 CD4+ T cell responses in the setting of fungal infection. However, the role of Dectin-1 signaling in neutrophils and its impact on CD4+ T cells is not well understood. In this study, we found that neutrophils stimulated with a Dectin-1 agonist diminish CD4+ T cell viability in a rapid and reactive oxygen species (ROS)-dependent manner. Furthermore, Dectin-1 promoted neutrophil PD-L1 expression via Syk and Card9 signaling, along with other immune-checkpoint factors in a neutrophil-biased manner. Although neutrophil PD-L1 did not significantly impact disease severity in experimental autoimmune encephalomyelitis (EAE), we found that CNS-infiltrated neutrophils potently up-regulate PD-L1 expression. Furthermore, a subset of PD-L1+ neutrophils was also found to express MHC-II during EAE. In summary, we found that Dectin-1 elicits a biphasic neutrophil response in which (1) T-cell suppressive ROS is followed by (2) up-regulation of PD-L1 expression. This response may serve to limit excess CD4+ T cell-driven inflammation in infection or autoimmunity while preserving host-defense functions of neutrophils.<\/jats:p><jats:p>Summary sentence: Mechanisms by which Dectin-1 signaling in neutrophils promotes a cellular phenotype with T cell-suppressive properties.<\/jats:p>","DOI":"10.1002\/jlb.3a0322-152rr","type":"journal-article","created":{"date-parts":[[2022,9,8]],"date-time":"2022-09-08T11:44:09Z","timestamp":1662637449000},"page":"1413-1425","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Dectin-1 signaling in neutrophils up-regulates PD-L1 and triggers ROS-mediated suppression of CD4+ T cells"],"prefix":"10.1093","volume":"112","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4061-5766","authenticated-orcid":false,"given":"M Elizabeth","family":"Deerhake","sequence":"first","affiliation":[{"name":"Department of Immunology, Duke University School of Medicine , Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emre D","family":"Cardakli","sequence":"additional","affiliation":[{"name":"Department of Immunology, Duke University School of Medicine , Durham, North Carolina, USA"},{"name":"Tri-Institutional MD-PhD Program, Weill Cornell Medical College, Rockefeller University and Memorial Sloan Kettering Cancer Center , New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari L","family":"Shinohara","sequence":"additional","affiliation":[{"name":"Department of Immunology, Duke University School of Medicine , Durham, North Carolina, USA"},{"name":"Department of Molecular Genetics and Microbiology, Duke University School of Medicine , Durham, North Carolina, 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