{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T12:50:47Z","timestamp":1784206247813,"version":"3.55.0"},"reference-count":34,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T00:00:00Z","timestamp":1772668800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T00:00:00Z","timestamp":1772668800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82073436"],"award-info":[{"award-number":["82073436"]}],"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":["82203917"],"award-info":[{"award-number":["82203917"]}],"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":["82373463"],"award-info":[{"award-number":["82373463"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Localized scleroderma (LoS) and systemic sclerosis (SSc) are both fibrotic diseases, but LoS is limited to the skin, whereas SSc involves systemic organ fibrosis. This study aimed to elucidate the mechanisms underlying these differences.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Skin biopsies from three healthy controls, three patients with LoS, and three patients with SSc underwent immunofluorescence and single\u2010cell RNA sequencing (scRNA\u2010seq). Key molecular functions were validated using in vitro assays and murine models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Immunofluorescence revealed a high prevalence of tertiary lymphoid structures (TLS) in LoS lesions (65.7%) compared with SSc (14.3%,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.0013). scRNA\u2010seq identified T follicular helper (Tfh) cells enriched within TLS in LoS. Tfh cells likely promote B cell recruitment via the\n                      <jats:italic>CXCL13\/CXCR5<\/jats:italic>\n                      axis, and integrin \u03b14 may support Tfh cell retention, contributing to TLS stability. These organized immune aggregates, together with elevated transforming growth factor \u03b2 (\n                      <jats:italic>TGF\u2010\u03b2<\/jats:italic>\n                      ) expression, may drive localized fibroblast activation and skin fibrosis in LoS. In contrast, SSc lesions contained fibroblasts with high CREB3L1 expression. CREB3L1 overexpression increased Type I collagen, fibronectin 1, and periostin levels in fibroblasts, whereas knockdown reduced them. In a SSc mouse model, CREB3L1 upregulation worsened skin and lung fibrosis, whereas knockdown alleviated it.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings suggest that LoS fibrosis is driven by TLS\u2010mediated local immune activation, whereas the systemic activation of CREB3L1\u2010expressing fibroblasts plays an important role in SSc fibrosis. Targeting local inflammation may benefit LoS, whereas targeting CREB3L1 offers a promising antifibrotic strategy in SSc.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.70039","type":"journal-article","created":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T09:40:52Z","timestamp":1766742052000},"page":"1152-1165","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Single\u2010Cell Profiling Reveals Divergent Mechanisms of Fibrosis in Localized Scleroderma and Systemic Sclerosis"],"prefix":"10.1002","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4084-9159","authenticated-orcid":false,"given":"Junxia","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Dermatology Zhongshan Hospital of Fudan University  Shanghai 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Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6411-0394","authenticated-orcid":false,"given":"Cheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Dermatology Zhongshan Hospital of Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linzhu","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Dermatology Zhongshan Hospital of Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqing","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Dermatology Zhongshan Hospital of Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feifei","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Dermatology Zhongshan Hospital of Fudan University  Shanghai 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