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This study presents key immune cell subsets and their interactions in the periphery in childhood Sj\u00f6gren\u2019s disease. Here we show that single-cell RNA sequencing identifies the subsets of IFN gene-enriched monocytes, <jats:italic>CD4<\/jats:italic><jats:sup>+<\/jats:sup> T effector memory, and <jats:italic>XCL1<\/jats:italic><jats:sup>+<\/jats:sup> NK cells as potential key players in childhood Sj\u00f6gren\u2019s disease, and especially in those with recurrent parotitis, which is the chief symptom prompting clinical visits from young children. A unique cluster of monocytes with type I and II IFN-related genes is identified in childhood Sj\u00f6gren\u2019s disease, compared to the age-matched control. In vitro regulatory T cell functional assay demonstrates intact functionality in childhood Sj\u00f6gren\u2019s disease in contrast to reduced suppression in adult Sj\u00f6gren\u2019s disease. Mapping this transcriptomic landscape and interplay of immune cell subsets will expedite the understanding of childhood Sj\u00f6gren\u2019s disease pathogenesis and set the foundation for precision medicine.<\/jats:p>","DOI":"10.1038\/s42003-024-06124-6","type":"journal-article","created":{"date-parts":[[2024,4,19]],"date-time":"2024-04-19T18:01:38Z","timestamp":1713549698000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Single-cell transcriptomics unveil profiles and interplay of immune subsets in rare autoimmune childhood Sj\u00f6gren\u2019s disease"],"prefix":"10.1038","volume":"7","author":[{"given":"Myung-Chul","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4478-791X","authenticated-orcid":false,"given":"Umasankar","family":"De","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Borcherding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joon","family":"Paek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Indraneel","family":"Bhattacharyya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Kolb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore","family":"Drashansky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akaluck","family":"Thatayatikom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8236-0346","authenticated-orcid":false,"given":"Weizhou","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3772-1832","authenticated-orcid":false,"given":"Seunghee","family":"Cha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,19]]},"reference":[{"key":"6124_CR1","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1056\/NEJMcp1702514","volume":"378","author":"X Mariette","year":"2018","unstructured":"Mariette, X. & Criswell, L. 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