{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T20:29:51Z","timestamp":1790281791625,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,12,13]],"date-time":"2019-12-13T00:00:00Z","timestamp":1576195200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007723","name":"Takeda Pharmaceuticals U.S.A.","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007723","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Scand J Immunol"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>CCR9\u00a0+\u00a0T helper (Th) cells can induce Sj\u00f6gren\u2010like symptoms in mice and both CCR9\u00a0+\u00a0Th cells and their ligand CCL25 are increased in the salivary glands of primary Sj\u00f6gren's syndrome (pSS) patients. Increased circulating CCR9\u00a0+\u00a0Th cells are present in pSS patients. CCR9\u00a0+\u00a0Th cells are hyperresponsive to IL\u20107, secrete high levels of IFN\u2010\u03b3, IL\u201021, IL\u201017 and IL\u20104 and potently stimulate B cells in both patients and healthy individuals. Our aim was to study co\u2010expression of chemokine receptors on CCR9\u00a0+\u00a0Th cells and whether in pSS this might differentially affect CCR9\u00a0+\u00a0Th cell frequencies. Frequencies of circulating CCR9\u00a0+\u00a0and CCR9\u2010 Th cells co\u2010expressing CXCR3, CCR4, CCR6 and CCR10 were studied in pSS patients and healthy controls. CCL25, CXCL10, CCL17, CCL20 and CCL27 mRNA and protein expression of salivary gland tissue of pSS and non\u2010Sj\u00f6gren's sicca (non\u2010SS) patients was assessed. Chemotaxis assays were performed to study migration induced by CXCL10 and CCL25. Higher expression of CXCR3, CCR4 and CCR6 but not CCR10 was observed on CCR9\u00a0+\u00a0Th cells as compared to cells lacking CCR9. Decreased frequencies of circulating memory CCR9\u00a0+\u00a0CXCR3+ Th cells were found in pSS patients, which was most pronounced in the effector memory subset. Increased salivary gland CCL25 and CXCL10 expression significantly correlated and both ligands functioned synergistically based on in vitro induced chemotaxis. Decreased memory CXCR3\u00a0+\u00a0CCR9+ Th cells in blood of pSS patients may be due to a concerted action of overexpressed ligands at the site of inflammation in the salivary glands facilitating their preferential migration and positioning in the lymphocytic infiltrates.<\/jats:p>","DOI":"10.1111\/sji.12852","type":"journal-article","created":{"date-parts":[[2019,11,16]],"date-time":"2019-11-16T14:45:30Z","timestamp":1573915530000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Decreased circulating CXCR3\u00a0+\u00a0CCR9+T helper cells are associated with elevated levels of their ligands CXCL10 and CCL25 in the salivary gland of patients with Sj\u00f6gren\u2019s syndrome to facilitate their concerted migration"],"prefix":"10.1111","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2506-2422","authenticated-orcid":false,"given":"Sofie L. M.","family":"Blokland","sequence":"first","affiliation":[{"name":"Department of Rheumatology &amp; Clinical Immunology University Medical Center Utrecht Utrecht University Utrecht The Netherlands"},{"name":"Department of Immunology Laboratory of Translational Immunology Utrecht University Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Kislat","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of D\u00fcsseldorf D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Homey","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of D\u00fcsseldorf D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glennda M.","family":"Smithson","sequence":"additional","affiliation":[{"name":"Takeda Pharmaceuticals International Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aike A.","family":"Kruize","sequence":"additional","affiliation":[{"name":"Department of Rheumatology &amp; Clinical Immunology University Medical Center Utrecht Utrecht University Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy R. 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