{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T09:54:16Z","timestamp":1780566856947,"version":"3.54.1"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82103736"],"award-info":[{"award-number":["82103736"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82073450"],"award-info":[{"award-number":["82073450"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National High Level Hospital Clinical Research Funding","award":["2022-PUMCH-A-066"],"award-info":[{"award-number":["2022-PUMCH-A-066"]}]},{"name":"National High Level Hospital Clinical Research Funding","award":["2022-PUMCH-B-092"],"award-info":[{"award-number":["2022-PUMCH-B-092"]}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["3332023012"],"award-info":[{"award-number":["3332023012"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"publisher","award":["2022YFC3601804"],"award-info":[{"award-number":["2022YFC3601804"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Key Clinical Specialty Project of China"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sweet syndrome (SS), also known as acute febrile neutrophilic dermatosis, is characterized by painful erythematous plaques or nodules with diffuse infiltration of mature neutrophils in the dermis. Most patients respond well to systemic corticosteroids, except for a few resistant cases. SS may be idiopathic or triggered by trauma, infection, drugs and immune disorders. The exact pathogenesis, pathophysiology and precise treatment options beyond corticosteroids remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>The objectives of this study were to gain a better understanding of the role of interleukin (IL)-36 signalling in SS and to examine the effect of treatment with spesolimab, an anti-IL-36R monoclonal antibody, in patients with SS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used spesolimab to treat two patients with SS and achieved favourable outcomes; however, the molecular mechanism of action involved in this treatment has not been proven. Here, we applied spatiotemporal transcriptomics at single-cell resolution and multiplex immunofluorescence on the skin lesion and blood samples from patients with SS before, during and after anti-IL-36R treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The release of neutrophil extracellular traps (NETs) was observed in the distinct NETosis neutrophil lineage infiltrating SS lesions, which secreted neutrophil elastase to splice full-length IL-36 proteins into their active forms, amplifying the inflammatory signal. The colocalized niches of neutrophils with heterogeneous maturation and IL36RN+ differentiated keratinocytes were found at dermoepidermal junction. The neutrophil-activated IL-36 signalling was considered as rapid inflammatory response and was eliminated after treatment. Meanwhile, CD8+ T cells were also recruited and participated in the interferon signalling and interacted with keratinocytes and neutrophils in the SS lesion, which was considered a delayed inflammatory response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Overall, a forward loop consisting of keratinocytes, neutrophils with heterogenous maturation and CD8+ T cells was constructed to decipher the potential pathogenesis of SS. IL-36 activated by neutrophil elastase released from these neutrophils was one of the drivers of the loop. Moreover, IL-36 signalling was confirmed as a novel and effective treatment target for SS, which may serve as an alternative option for corticosteroid-resistant cases and patients with contraindications.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bjd\/ljaf396","type":"journal-article","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T12:03:21Z","timestamp":1760097801000},"page":"311-325","source":"Crossref","is-referenced-by-count":5,"title":["Spatiotemporal transcriptomics deciphered neutrophil-activated interleukin-36 as driver and effective\u00a0therapeutic target in Sweet syndrome"],"prefix":"10.1093","volume":"194","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1678-6338","authenticated-orcid":false,"given":"Yifan","family":"Fu","sequence":"first","affiliation":[{"name":"Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyu","family":"Pang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiejun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Medical College , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiannan","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuehua","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongchun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5065-4086","authenticated-orcid":false,"given":"Hanlin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sifan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jindi","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Plastic and Aesthetic Surgery, The Second Affiliated Hospital of Harbin Medical University , Harbin ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Plastic and Aesthetic Surgery, The Second Affiliated Hospital of Harbin Medical University , Harbin ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feifan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Computer Science, University College London , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"Beijing Advanced Innovation Centre for Biomedical Engineering, Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Engineering Medicine, Beihang University , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongzhong","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,10,22]]},"reference":[{"key":"2026012706473997600_ljaf396-B1","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1056\/NEJMicm1911025","article-title":"Sweet\u2019s syndrome","volume":"382","author":"Pulido-P\u00e9rez","year":"2020","journal-title":"N Engl J 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