{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T17:52:10Z","timestamp":1793987530383,"version":"4.8.0"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,3,19]],"date-time":"2021-03-19T00:00:00Z","timestamp":1616112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81771764"],"award-info":[{"award-number":["81771764"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013290","name":"National Key Research and Development Program of China Stem Cell and Translational Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013290","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p><jats:bold>Objectives:<\/jats:bold> To explore the potential role of CD3<jats:sup>+<\/jats:sup>CD8<jats:sup>+<\/jats:sup>CD161<jats:sup>high<\/jats:sup> TCRV\u03b17.2<jats:sup>+<\/jats:sup> mucosal-associated invariant T (MAIT) cells in the pathogenesis of primary biliary cholangitis (PBC).<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> We enrolled 55 patients with PBC, 69 healthy controls (HCs), and 8 patients with hepatic hemangioma. Circulating MAIT cells and their chemokine receptor profiles and cytokine production were quantified using flow cytometry. Liver-resident MAIT cells were examined by immunofluorescence staining. CXCL12-mediated chemotaxis of MAIT cells was measured using a transwell migration assay. Plasma interleukin (IL)-18 was measured using ELISA, and cytokine production in IL-18-stimulated MAIT cells was detected using flow cytometry.<\/jats:p><jats:p><jats:bold>Result:<\/jats:bold> Peripheral MAIT cells were found to be significantly lower in patients with PBC (3.0 \u00b1 3.2% vs. 9.4 \u00b1 8.0%, <jats:italic>p<\/jats:italic> &amp;lt; 0.01) and negatively correlated with alkaline phosphatase (ALP) levels (<jats:italic>r<\/jats:italic> = \u22120.3209, <jats:italic>p<\/jats:italic> &amp;lt; 0.05). Liver immunofluorescence staining suggested that MAIT cells might accumulate in PBC liver. MAIT cells from patients with PBC expressed higher levels of CXCR4 (84.8 \u00b1 18.0% vs. 58.7 \u00b1 11.4%, <jats:italic>p<\/jats:italic> &amp;lt; 0.01), and the expression of CXCL12 was higher in PBC liver. CXCL12 promoted MAIT cell chemotaxis (70.4 \u00b1 6.8% vs. 52.2 \u00b1 3.5%, <jats:italic>p<\/jats:italic> &amp;lt; 0.01), which was attenuated by CXCR4 antagonist. MAIT cells from PBC produced significantly more interferon-\u03b3 (IFN-\u03b3) (88.3 \u00b1 4.2% vs. 64.2 \u00b1 10.1%, <jats:italic>p<\/jats:italic> &amp;lt; 0.01), tumor necrosis factor-\u03b1 (TNF-\u03b1) (93.0 \u00b1 1.1% vs. 80.1 \u00b1 5.3%, <jats:italic>p<\/jats:italic> &amp;lt; 0.01), Granzyme B (89.3 \u00b1 3.3% vs. 72.1 \u00b1 7.0%, <jats:italic>p<\/jats:italic> &amp;lt; 0.01), and perforin (46.8 \u00b1 6.6% vs. 34.8 \u00b1 7.7%, <jats:italic>p<\/jats:italic> &amp;lt; 0.05). MAIT cells from PBC expressed higher levels of IL18-R\u03b1 (83.8 \u00b1 10.2% vs. 58.3 \u00b1 8.7%, <jats:italic>p<\/jats:italic> &amp;lt; 0.01). Plasma IL-18 was more abundant in patients with PBC (286.8 \u00b1 75.7 pg\/ml vs. 132.9 \u00b1 78.1 pg\/ml, <jats:italic>p<\/jats:italic> &amp;lt; 0.01). IL-18 promoted IFN-\u03b3 production in MAIT cells (74.9 \u00b1 6.6% vs. 54.7 \u00b1 6.7%, <jats:italic>p<\/jats:italic> &amp;lt; 0.01), which was partially attenuated by blocking IL-18R (68.6 \u00b1 8.3% vs. 43.5 \u00b1 4.2%, <jats:italic>p<\/jats:italic> &amp;lt; 0.01).<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Mucosal-associated invariant T cells from patients with PBC accumulated in the liver <jats:italic>via<\/jats:italic> CXCL12-CXCR4-mediated chemotaxis, produced pro-inflammatory cytokines, and contributed to portal inflammation, which was potentially mediated by elevated IL-18. Targeting MAIT cells might be a therapeutic approach for PBC.<\/jats:p>","DOI":"10.3389\/fimmu.2021.578548","type":"journal-article","created":{"date-parts":[[2021,3,19]],"date-time":"2021-03-19T05:39:45Z","timestamp":1616132385000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["CXCL12-CXCR4-Mediated Chemotaxis Supports Accumulation of Mucosal-Associated Invariant T Cells Into the Liver of Patients With 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