{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T15:13:09Z","timestamp":1793113989659,"version":"4.5.0"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T00:00:00Z","timestamp":1708387200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T00:00:00Z","timestamp":1708387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21K08436"],"award-info":[{"award-number":["21K08436"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arthritis Res Ther"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Objectives<\/jats:title>\n                <jats:p>IgG4-related disease (IgG4-RD) is a systemic autoimmune disease with an unknown etiology, affecting single\/multiple organ(s). Pathological findings include the infiltration of IgG4-producing plasma cells, obliterative phlebitis, and storiform fibrosis. Although immunological studies have shed light on the dysregulation of lymphocytes in IgG4-RD pathogenesis, the role of non-immune cells remains unclear. This study aimed to investigate the demographics and characteristics of non-immune cells in IgG4-RD and explore potential biomarkers derived from non-immune cells in the sera.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We conducted single-cell RNA sequence (scRNA-seq) on non-immune cells isolated from submandibular glands of IgG4-RD patients. We focused on fibroblasts expressing collagen type XV and confirmed the presence of those fibroblasts using immunohistochemistry. Additionally, we measured the levels of collagen type XV in the sera of IgG4-RD patients.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The scRNA-seq analysis revealed several distinct clusters consisting of fibroblasts, endothelial cells, ductal cells, and muscle cells. Differential gene expression analysis showed upregulation of <jats:italic>COL15A1<\/jats:italic> in IgG4-RD fibroblasts compared to control subjects. Notably, <jats:italic>COL15A1<\/jats:italic>-positive fibroblasts exhibited a distinct transcriptome compared to <jats:italic>COL15A1<\/jats:italic>-negative counterparts. Immunohistochemical analysis confirmed a significant presence of collagen type XV-positive fibroblasts in IgG4-RD patients. Furthermore, immune-suppressive therapy in active IgG4-RD patients resulted in decreased serum levels of collagen type XV.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Our findings suggest that collagen type XV-producing fibroblasts may represent a disease-characterizing non-immune cell population in IgG4-RD and hold potential as a disease-monitoring marker.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13075-024-03289-7","type":"journal-article","created":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T10:02:39Z","timestamp":1708423359000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Single-cell RNA sequencing of submandibular gland reveals collagen type XV-positive fibroblasts as a disease-characterizing cell population of IgG4-related disease"],"prefix":"10.1186","volume":"26","author":[{"given":"Shigeru","family":"Tanaka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuya","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arifumi","family":"Iwata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Kiuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kota","family":"Kokubo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohisa","family":"Iinuma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Sugiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toyoyuki","family":"Hanazawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyoshi","family":"Hirahara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kei","family":"Ikeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Nakajima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,2,20]]},"reference":[{"issue":"6","key":"3289_CR1","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1056\/NEJMra1104650","volume":"366","author":"JH Stone","year":"2012","unstructured":"Stone JH, Zen Y, Deshpande V. 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