{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T13:05:56Z","timestamp":1770901556439,"version":"3.50.1"},"reference-count":47,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T00:00:00Z","timestamp":1770854400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007045","name":"SECIHTI","doi-asserted-by":"publisher","award":["273324"],"award-info":[{"award-number":["273324"]}],"id":[{"id":"10.13039\/501100007045","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Circulant follicular helper T cells (cTfh) are a specialized subset of CD4+ T cells that induce immunoglobulin class switching and antibody secretion in plasma cells through the production of IL-21. To investigate the role of cTfh-like cells in the development of Sj\u00f6gren\u2019s disease (SjD), we analyzed the circulating Tfh-like cells, their production of IL-21 and IL-4, and the co-expression of ICOS, CXCR5, and CCR9 by flow cytometry, and evaluated their association with clinical characteristics of the disease. Percentages of CD4+ IL-21+ CXCR5+ ICOS+ CCR9+ IL-4+ T cells were analyzed in peripheral blood samples from 20 healthy controls (HCs) and 19 patients with SjD. Serum levels of IL-1\u03b2, IL-4, IL-6, IL-21, and sCD40L were assessed using a Luminex assay. Laboratory data included anti-Ro\/La antibodies, immunoglobulin levels (IgA and IgG), focus score, disease duration, and ESDDAI\/SSDDI scores. Decreased frequencies of CXCR5+ IL-21+ T cells and CCR9+ IL-4+ T cells were observed in the peripheral blood of patients with SjD. Heatmap analysis was used to identify correlations between cTfh-like cells and clinical parameters. Elevated proportions of cTfh-like cells were positively correlated with disease severity, inflammatory markers, and autoantibody production. High-dimensional analysis identified distinct subpopulations with differential expression of ICOS, CXCR5, CCR9 and IL-21, suggesting heterogeneity of these cells in SjD and their involvement in disease pathogenesis.<\/jats:p>","DOI":"10.3390\/ijms27041765","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T12:05:46Z","timestamp":1770897946000},"page":"1765","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Analysis of CCR9, CXCR5 and ICOS in Circulating Follicular Helper T Cell-like Populations in Sj\u00f6gren\u2019s Disease"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6050-5471","authenticated-orcid":false,"given":"Jose Antonio","family":"Garcia-Espinoza","sequence":"first","affiliation":[{"name":"Doctorado en Ciencias Biom\u00e9dicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico"},{"name":"Facultad de Ciencias de la Salud, Universidad An\u00e1huac, Campus Norte, Huixquilucan 52786, Estado de Mexico, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7344-1283","authenticated-orcid":false,"given":"Erika Fabiola","family":"L\u00f3pez-Villalobos","sequence":"additional","affiliation":[{"name":"Laboratorio de An\u00e1lisis Cl\u00ednicos y Bacteriol\u00f3gicos (Vinculaci\u00f3n), Centro Universitario de Ciencias Exactas e Ingenier\u00edas, Universidad de Guadalajara, Guadalajara 44430, Jalisco, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariel","family":"Garc\u00eda-Chagoll\u00e1n","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n en Ciencias Biom\u00e9dicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2294-200X","authenticated-orcid":false,"given":"Jefte Felipe","family":"Uribe-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Servicio de Reumatolog\u00eda, Hospital Civil \u201cFray Antonio Alcalde\u201d, Guadalajara 44200, Jalisco, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0082-4892","authenticated-orcid":false,"given":"Santiago","family":"Torres-Liz\u00e1rraga","sequence":"additional","affiliation":[{"name":"Servicio de Reumatolog\u00eda, Hospital Civil \u201cFray Antonio Alcalde\u201d, Guadalajara 44200, Jalisco, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2272-9260","authenticated-orcid":false,"given":"Jos\u00e9 Francisco","family":"Mu\u00f1oz-Valle","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n en Ciencias Biom\u00e9dicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gloria Esther","family":"Mart\u00ednez-Bonilla","sequence":"additional","affiliation":[{"name":"Servicio de Reumatolog\u00eda, Hospital Civil \u201cFray Antonio Alcalde\u201d, Guadalajara 44200, Jalisco, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergio","family":"Cerpa-Cruz","sequence":"additional","affiliation":[{"name":"Servicio de Reumatolog\u00eda, Hospital Civil \u201cFray Antonio Alcalde\u201d, Guadalajara 44200, Jalisco, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0836-4186","authenticated-orcid":false,"given":"Claudia Azucena","family":"Palafox-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n en Ciencias Biom\u00e9dicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1658-8630","authenticated-orcid":false,"given":"Miguel","family":"Mar\u00edn-Rosales","sequence":"additional","affiliation":[{"name":"Servicio de Reumatolog\u00eda, Hospital General de Occidente, Zapop\u00e1n 45170, Jalisco, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6010-0837","authenticated-orcid":false,"given":"Edith","family":"Oregon-Romero","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n en Ciencias Biom\u00e9dicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,12]]},"reference":[{"key":"ref_1","first-page":"2211","article-title":"Sj\u00f6gren\u2019s 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