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Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Chronic rhinosinusitis (CRS) is a chronic inflammatory disease with an autoimmune background. Altered expression levels of T cell immunoglobulin and mucin-domain containing-3 (TIM-3), C-X-C chemokine receptor type 5 (CXCR5), and programmed cell death protein 1 (PD-1) are implicated in the progression of inflammatory and autoimmune diseases. Moreover, CXCR5<jats:sup>+<\/jats:sup>TIM-3<jats:sup>-<\/jats:sup>PD-1<jats:sup>+<\/jats:sup> stem-like cytotoxic T cells function as memory stem cells during chronic disease processes and retain cytotoxicity-related gene networks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To explore the expressions of CXCR5, TIM-3, and PD-1 on T cells and their correlation with clinical parameters in CRS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Flow cytometry was used to assess the expressions and co-expressions of CXCR5, TIM-3, and PD-1 on T cells in the tissues of the paranasal sinus and peripheral blood of patients with CRS as well as healthy controls. Immunofluorescence was used to assess the co-localization of TIM-3, CXCR5, and PD-1 with T cells. The disease severity of our patients with CRS was evaluated using the Lund-Mackay score. A complete blood count was also performed for the patients with CRS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Expression levels of CXCR5 and PD-1 on T cells were significantly increased in the nasal tissues of patients with CRS. Compared with those in healthy controls, patients with CRS had high percentages of CXCR5<jats:sup>+<\/jats:sup>TIM-3<jats:sup>-<\/jats:sup>PD-1<jats:sup>+<\/jats:sup> CD8<jats:sup>+<\/jats:sup> and CD4<jats:sup>+<\/jats:sup> T cells in nasal tissues, while no significant difference was observed in peripheral blood levels. Patients with CRS had a higher density of nasal CXCR5+TIM-3-PD-1+ T cells than that in healthy controls. CXCR5<jats:sup>+<\/jats:sup>TIM-3<jats:sup>-<\/jats:sup>PD-1<jats:sup>+<\/jats:sup> CD8<jats:sup>+<\/jats:sup> T cell levels in the nasal polyps of patients with CRS were negatively correlated with the patients\u2019 Lund-Mackay scores. The levels of CXCR5<jats:sup>+<\/jats:sup>TIM-3<jats:sup>-<\/jats:sup>PD-1<jats:sup>+<\/jats:sup> T cells in nasal tissues were also negatively associated with disease duration and positively associated with the chronic inflammatory state of CRS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The level of CXCR5<jats:sup>+<\/jats:sup>TIM-3<jats:sup>-<\/jats:sup>PD-1<jats:sup>+<\/jats:sup> stem cell-like T cells, especially CXCR5+TIM-3-PD-1+ CD8+ T cells, is increased in CRS. Therefore, inducing CXCR5<jats:sup>+<\/jats:sup>TIM-3<jats:sup>-<\/jats:sup>PD-1<jats:sup>+<\/jats:sup> T cell exhaustion may be an effective immunotherapy for CRS.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1295309","type":"journal-article","created":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T04:40:02Z","timestamp":1707972002000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["CXCR5+TIM-3-PD-1+ stem-like cytotoxic CD8+ T cells: elevated in chronic rhinosinusitis and associated with disease 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