{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T14:12:30Z","timestamp":1789567950901,"version":"build-2803163510"},"reference-count":33,"publisher":"American Society for Clinical Investigation","issue":"20","license":[{"start":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T00:00:00Z","timestamp":1760486400000},"content-version":"vor","delay-in-days":57,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"crossref","award":["R01AR079483"],"award-info":[{"award-number":["R01AR079483"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"crossref","award":["I01RX002701"],"award-info":[{"award-number":["I01RX002701"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Berstein Foundation","award":["None"],"award-info":[{"award-number":["None"]}]},{"name":"Edwin and Fanny Gray Hall Center for Human Appearance","award":["None"],"award-info":[{"award-number":["None"]}]},{"name":"H.T. Leung Foundation","award":["None"],"award-info":[{"award-number":["None"]}]},{"DOI":"10.13039\/100001582","name":"Dermatology Foundation","doi-asserted-by":"crossref","award":["Career Development Award"],"award-info":[{"award-number":["Career Development Award"]}],"id":[{"id":"10.13039\/100001582","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,15]]},"abstract":"<jats:p>Sweet syndrome (also known as acute febrile neutrophilic dermatosis) is a rare inflammatory skin disorder characterized by erythematous plaques with a dense dermal neutrophilic infiltrate. The first-line therapy remains oral corticosteroids, which suppresses inflammation nonspecifically. Although neutrophils are typically short-lived, how they persist in Sweet syndrome skin and contribute to disease pathogenesis remains unclear. Here, we identify a previously unrecognized population of antigen-presenting cell\u2013like (APC-like) neutrophils expressing MHC class II genes that are uniquely present in Sweet syndrome skin but absent in healthy tissue and the circulation. Keratinocytes extended neutrophil lifespan 10-fold in coculture experiments and drove the emergence of an APC-like phenotype in approximately 30% of neutrophils, mirroring observations in patients\u2019 lesions. Mechanistically, keratinocyte-derived serum amyloid A1 (SAA1) signals through the formyl peptide receptor 2 (FPR2) on neutrophils to promote their survival. These long-lived neutrophils actively orchestrate local immune responses by recruiting T cells and inducing cytokine production. Strikingly, dual blockade of SAA1\/FPR2 signaling restores neutrophil turnover to baseline levels, with efficacy comparable to high-dose corticosteroids. These findings uncover a keratinocyte\/neutrophil\/T cell axis that sustains chronic inflammation in Sweet syndrome and highlight the SAA1\/FPR2 pathway as a promising target for precision therapy.<\/jats:p>","DOI":"10.1172\/jci193566","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T16:00:43Z","timestamp":1755619243000},"source":"Crossref","is-referenced-by-count":8,"title":["SAA1\/FPR2 signaling between keratinocytes and neutrophils sustains chronic inflammation in Sweet syndrome"],"prefix":"10.1172","volume":"135","author":[{"given":"Jianhe","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA."},{"name":"Corporal Michael Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satish","family":"Sati","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Ahart","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Rapp-Reyes","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2517-7008","authenticated-orcid":true,"given":"Robert G.","family":"Micheletti","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William D.","family":"James","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA."},{"name":"Corporal Michael Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misha","family":"Rosenbach","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, 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