{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:16:22Z","timestamp":1791994582401,"version":"4.4.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T00:00:00Z","timestamp":1744156800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82430100"],"award-info":[{"award-number":["82430100"]}],"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":["82273514"],"award-info":[{"award-number":["82273514"]}],"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":["82173407"],"award-info":[{"award-number":["82173407"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020732","name":"Innovative Research Team of High-Level Local Universities in Shanghai","doi-asserted-by":"publisher","award":["SHSMU-ZDCX20211002"],"award-info":[{"award-number":["SHSMU-ZDCX20211002"]}],"id":[{"id":"10.13039\/100020732","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Pemphigus is a life-threatening autoimmune disease mediated by anti-desmoglein (Dsg) autoantibodies. Ectopic lymphoid-like structures (ELS) are frequently found in chronic skin lesions and are thought to contribute to local autoantibody production. However, the mechanisms driving ELS formation at lesion sites remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To investigate the role of myeloid cells in the formation of ELS in pemphigus lesions, and to identify potential therapeutic targets by better understanding the underlying mechanisms that contribute to this process.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used single-cell RNA sequencing (scRNA-seq) to identify the myeloid subpopulations in pemphigus lesions and study their functions. Immunohistochemistry (IHC), immunofluorescence and flow cytometry were used to validate the presence of interleukin (IL)-1\u03b2-producing myeloid cells. Culture, bulk RNA-seq and transwell chemotaxis experiments were conducted to assess the effects of IL-34 and tumour necrosis factor (TNF)-\u03b1 on monocytes. Additionally, the high expression of IL-34 in pemphigus keratinocytes was validated by IHC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We first confirmed the abundant presence of myeloid cells within ELS in pemphigus skin lesions, including pemphigus vulgaris and pemphigus foliaceus. Single-cell RNA-seq revealed that IL-1\u03b2-producing macrophages (\u2018IL1B_Macro\u2019) is the dominant myeloid subpopulation in pemphigus lesions, originating from classical monocytes. These cells have a strong inflammatory and chemotactic transcriptomic profile, expressing high levels of IL-1\u03b2, IL-6 and chemokines such as CCL20, CCL3, CCL5 and CXCL5, promoting leucocyte infiltration. Ex vivo experiments showed that IL1B_Macro differentiation is enhanced by the synergistic action of IL-34 and TNF-\u03b1, which can be attenuated by a colony-stimulating factor 1 receptor (CSF-1R) inhibitor. IL-34 alone also promotes IL-1\u03b2 and CCL20 expression, and keratinocytes were found to be the major source of elevated IL-34 in pemphigus lesions. Bulk RNA-seq data indicated that high IL-34 expression in pemphigus keratinocytes correlates with increased levels of CCL5, IL-6 and IL-23\u03b1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>IL-1\u03b2-producing myeloid cells play a crucial role in the formation of ELS in pemphigus lesions through inflammatory and chemotactic pathways. Keratinocytes contribute to this process by producing IL-34, which fuels local inflammation. These findings offer new insights into pemphigus immunopathogenesis and suggest the IL-34\/CSF-1R pathway as a potential therapeutic target.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bjd\/ljaf130","type":"journal-article","created":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T07:27:35Z","timestamp":1744183655000},"page":"287-297","source":"Crossref","is-referenced-by-count":7,"title":["Interleukin (IL)-34 promotes the inflammatory role of IL-1\u03b2-producing myeloid cells in pemphigus lesions"],"prefix":"10.1093","volume":"193","author":[{"given":"Zixuan","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Dermatology, Center for Immune-Related Diseases at Shanghai Institute of Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4745-5611","authenticated-orcid":false,"given":"Wenzhe","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Center for Immune-Related Diseases at Shanghai Institute of Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuqiao","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Center for Immune-Related Diseases at Shanghai Institute of Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Center for Immune-Related Diseases at Shanghai Institute of Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanxin","family":"Huang","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Biliary Tract Disease Research, Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai ,","place":["China"]},{"name":"Faculty of Basic Medicine, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine , Shanghai ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiqin","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Center for Immune-Related Diseases at Shanghai Institute of Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Center for Immune-Related Diseases at Shanghai Institute of Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,4,9]]},"reference":[{"key":"2025071703174107500_ljaf130-B1","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1080\/08916930600971505","article-title":"Desmoglein autoimmunity in the pathogenesis of pemphigus","volume":"39","author":"Gniadecki","year":"2006","journal-title":"Autoimmunity"},{"key":"2025071703174107500_ljaf130-B2","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1016\/S0140-6736(19)31778-7","article-title":"Pemphigus","volume":"394","author":"Schmidt","year":"2019","journal-title":"Lancet"},{"key":"2025071703174107500_ljaf130-B3","doi-asserted-by":"crossref","first-page":"103128","DOI":"10.1016\/j.jaut.2023.103128","article-title":"Integrative single-cell analysis reveals distinct adaptive immune signatures in the cutaneous lesions of pemphigus","volume":"142","author":"Xu","year":"2023","journal-title":"J Autoimmun"},{"key":"2025071703174107500_ljaf130-B4","doi-asserted-by":"crossref","first-page":"2362","DOI":"10.1016\/j.jid.2017.05.032","article-title":"Pivotal role of lesional and perilesional T\/B lymphocytes in pemphigus pathogenesis","volume":"137","author":"Yuan","year":"2017","journal-title":"J Invest Dermatol"},{"key":"2025071703174107500_ljaf130-B5","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.jid.2019.07.717","article-title":"Autoreactive B cell differentiation in diffuse ectopic lymphoid-like structures of inflamed pemphigus lesions","volume":"140","author":"Zhou","year":"2020","journal-title":"J Invest Dermatol"},{"key":"2025071703174107500_ljaf130-B6","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.1016\/j.jid.2021.01.030","article-title":"The pathogenic role of CD4+ tissue-resident memory T cells bearing T follicular helper-like phenotype in pemphigus lesions","volume":"141","author":"Zou","year":"2021","journal-title":"J Invest Dermatol"},{"key":"2025071703174107500_ljaf130-B7","doi-asserted-by":"crossref","first-page":"117","DOI":"10.7150\/thno.48624","article-title":"Tertiary lymphoid organs are associated with the progression of kidney damage and regulated by interleukin-17A","volume":"11","author":"Luo","year":"2021","journal-title":"Theranostics"},{"key":"2025071703174107500_ljaf130-B8","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1038\/nri2832","article-title":"New insights into the development of lymphoid tissues","volume":"10","author":"van de Pavert","year":"2010","journal-title":"Nat Rev Immunol"},{"key":"2025071703174107500_ljaf130-B9","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/j.immuni.2004.09.006","article-title":"Induction of secondary and tertiary lymphoid structures in the skin","volume":"21","author":"Cupedo","year":"2004","journal-title":"Immunity"},{"key":"2025071703174107500_ljaf130-B10","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1146\/annurev.immunol.26.021607.090257","article-title":"Development of secondary lymphoid organs","volume":"26","author":"Randall","year":"2008","journal-title":"Annu Rev Immunol"},{"key":"2025071703174107500_ljaf130-B11","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1146\/annurev-cellbio-111315-125306","article-title":"Emergence and evolution of secondary lymphoid organs","volume":"32","author":"Neely","year":"2016","journal-title":"Annu Rev Cell Dev Biol"},{"key":"2025071703174107500_ljaf130-B12","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1084\/jem.20181216","article-title":"Type I interferon induces CXCL13 to support ectopic germinal center formation","volume":"216","author":"Denton","year":"2019","journal-title":"J Exp Med"},{"key":"2025071703174107500_ljaf130-B13","doi-asserted-by":"crossref","first-page":"850998","DOI":"10.3389\/fimmu.2022.850998","article-title":"Role of the CXCL13\/CXCR5 axis in autoimmune diseases","volume":"13","author":"Pan","year":"2022","journal-title":"Front Immunol"},{"key":"2025071703174107500_ljaf130-B14","doi-asserted-by":"crossref","first-page":"2022","DOI":"10.1038\/s41467-022-29701-x","article-title":"Loss of vascular endothelial notch signaling promotes spontaneous formation of tertiary lymphoid structures","volume":"13","author":"Fleig","year":"2022","journal-title":"Nat Commun"},{"key":"2025071703174107500_ljaf130-B15","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.coi.2005.11.008","article-title":"The mononuclear phagocyte system","volume":"18","author":"Hume","year":"2006","journal-title":"Curr Opin Immunol"},{"key":"2025071703174107500_ljaf130-B16","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1146\/annurev-pathmechdis-012418-012718","article-title":"Diversity, mechanisms, and significance of macrophage plasticity","volume":"15","author":"Locati","year":"2020","journal-title":"Annu Rev Pathol"},{"key":"2025071703174107500_ljaf130-B17","doi-asserted-by":"crossref","first-page":"6425","DOI":"10.1002\/jcp.26429","article-title":"Macrophage plasticity, polarization, and function in health and disease","volume":"233","author":"Shapouri-Moghaddam","year":"2018","journal-title":"J Cell Physiol"},{"key":"2025071703174107500_ljaf130-B18","doi-asserted-by":"crossref","first-page":"734008","DOI":"10.3389\/fimmu.2021.734008","article-title":"Macrophage polarization and plasticity in systemic lupus erythematosus","volume":"12","author":"Ahamada","year":"2021","journal-title":"Front Immunol"},{"key":"2025071703174107500_ljaf130-B19","doi-asserted-by":"crossref","first-page":"3021","DOI":"10.1182\/blood-2004-02-0701","article-title":"Monocyte-like and mature macrophages produce CXCL13 (B cell-attracting chemokine 1) in inflammatory lesions with lymphoid neogenesis","volume":"104","author":"Carlsen","year":"2004","journal-title":"Blood"},{"key":"2025071703174107500_ljaf130-B20","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1093\/cvr\/cvt263","article-title":"M1 macrophages act as LT\u03b2R-independent lymphoid tissue inducer cells during atherosclerosis-related lymphoid neogenesis","volume":"101","author":"Guedj","year":"2014","journal-title":"Cardiovasc Res"},{"key":"2025071703174107500_ljaf130-B21","doi-asserted-by":"crossref","first-page":"102846","DOI":"10.1016\/j.autrev.2021.102846","article-title":"CCR6\u2013CCL20 axis as a therapeutic target for autoimmune diseases","volume":"20","author":"Meitei","year":"2021","journal-title":"Autoimmun Rev"},{"key":"2025071703174107500_ljaf130-B22","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1046\/j.1365-4362.2001.01083.x","article-title":"TNFalpha and IL-6 are mediators in the blistering process of pemphigus","volume":"40","author":"L\u00f3pez-Robles","year":"2001","journal-title":"Int J Dermatol"},{"key":"2025071703174107500_ljaf130-B23","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1038\/cdd.2010.60","article-title":"IL-34 and M-CSF share the receptor Fms but are not identical in biological activity and signal activation","volume":"17","author":"Chihara","year":"2010","journal-title":"Cell Death Diff"},{"key":"2025071703174107500_ljaf130-B24","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1038\/ni.2360","article-title":"IL-34 is a tissue-restricted ligand of CSF1R required for the development of Langerhans cells and microglia","volume":"13","author":"Wang","year":"2012","journal-title":"Nat Immunol"},{"key":"2025071703174107500_ljaf130-B25","doi-asserted-by":"crossref","first-page":"114703","DOI":"10.1016\/j.ejmech.2022.114703","article-title":"Discovery of small-molecules targeting the CCL20\/CCR6 axis as first-class inhibitors for inflammatory bowel diseases","volume":"243","author":"Martina","year":"2022","journal-title":"Eur J Med Chem"},{"key":"2025071703174107500_ljaf130-B26","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1023\/B:JOCI.0000018066.46279.6b","article-title":"Increased expression of CCL20 in human inflammatory bowel disease","volume":"24","author":"Kaser","year":"2004","journal-title":"J Clin Immunol"},{"key":"2025071703174107500_ljaf130-B27","doi-asserted-by":"crossref","first-page":"2803","DOI":"10.1084\/jem.20071397","article-title":"Preferential recruitment of CCR6-expressing Th17 cells to inflamed joints via CCL20 in rheumatoid arthritis and its animal model","volume":"204","author":"Hirota","year":"2007","journal-title":"J Exp Med"},{"key":"2025071703174107500_ljaf130-B28","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1038\/nm.3432","article-title":"Pathogenic conversion of Foxp3+ T cells into TH17 cells in autoimmune arthritis","volume":"20","author":"Komatsu","year":"2014","journal-title":"Nat Med"},{"key":"2025071703174107500_ljaf130-B29","doi-asserted-by":"crossref","first-page":"2358","DOI":"10.1016\/j.jaci.2020.11.008","article-title":"Immunophenotyping in pemphigus reveals a T(H)17\/T(FH)17 cell-dominated immune response promoting desmoglein1\/3-specific autoantibody production","volume":"147","author":"Holstein","year":"2021","journal-title":"J Allergy Clin Immunol"},{"key":"2025071703174107500_ljaf130-B30","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1186\/s12967-022-03387-7","article-title":"Transcriptomic profiling of pemphigus lesion infiltrating mononuclear cells reveals a distinct local immune microenvironment and novel lncRNA regulators","volume":"20","author":"Huang","year":"2022","journal-title":"J Transl Med"},{"key":"2025071703174107500_ljaf130-B31","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1684\/ejd.2013.2177","article-title":"The imbalance of Th17 and regulatory T cells in pemphigus patients","volume":"23","author":"Xu","year":"2013","journal-title":"Eur J Dermatol"},{"key":"2025071703174107500_ljaf130-B32","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/s41586-023-06685-2","article-title":"IL-1\u03b2+ macrophages fuel pathogenic inflammation in pancreatic cancer","volume":"623","author":"Caronni","year":"2023","journal-title":"Nature"},{"key":"2025071703174107500_ljaf130-B33","doi-asserted-by":"crossref","first-page":"22239","DOI":"10.1038\/s41598-020-79312-z","article-title":"Effect of IL-34 on T helper 17 cell proliferation and IL-17 secretion by peripheral blood mononuclear cells from rheumatoid arthritis patients","volume":"10","author":"Li","year":"2020","journal-title":"Sci Rep"},{"key":"2025071703174107500_ljaf130-B34","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/s40425-017-0257-y","article-title":"Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy","volume":"5","author":"Cannarile","year":"2017","journal-title":"J Immunother Cancer"}],"container-title":["British Journal of Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bjd\/advance-article-pdf\/doi\/10.1093\/bjd\/ljaf130\/62899252\/ljaf130.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bjd\/article-pdf\/193\/2\/287\/62899252\/ljaf130.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bjd\/article-pdf\/193\/2\/287\/62899252\/ljaf130.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T07:17:54Z","timestamp":1752736674000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bjd\/article\/193\/2\/287\/8109440"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,9]]},"references-count":34,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,4,9]]},"published-print":{"date-parts":[[2025,7,17]]}},"URL":"https:\/\/doi.org\/10.1093\/bjd\/ljaf130","relation":{},"ISSN":["0007-0963","1365-2133"],"issn-type":[{"value":"0007-0963","type":"print"},{"value":"1365-2133","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,8]]},"published":{"date-parts":[[2025,4,9]]}}}