{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T19:35:54Z","timestamp":1781811354585,"version":"3.54.5"},"reference-count":73,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,5,30]],"date-time":"2024-05-30T00:00:00Z","timestamp":1717027200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oral. Health"],"abstract":"<jats:p>In a murine model (LC<jats:sup>\u0394MHC-II<\/jats:sup>) designed to abolish MHC-II expression in Langerhans cells (LCs), \u223c18% of oral LCs retain MHC-II, yet oral mucosal CD4 T cells numbers are unaffected. In LC<jats:sup>\u0394MHC-II<\/jats:sup> mice, we now show that oral intraepithelial conventional CD8\u03b1\u03b2 T cell numbers expand 30-fold. Antibody-mediated ablation of CD4 T cells in wild-type mice also resulted in CD8\u03b1\u03b2 T cell expansion in the oral mucosa. Therefore, we <jats:italic>hypothesize<\/jats:italic> that MHC class II molecules uniquely expressed on Langerhans cells mediate the suppression of intraepithelial resident-memory CD8 T cell numbers via a CD4 T cell-dependent mechanism. The expanded oral CD8 T cells co-expressed CD69 and CD103 and the majority produced IL-17A [CD8 T cytotoxic (Tc)17 cells] with a minority expressing IFN-\u03b3 (Tc1 cells). These oral CD8 T cells showed broad T cell receptor V\u03b2 gene usage indicating responsiveness to diverse oral antigens. Generally supporting Tc17 cells, transforming growth factor-\u03b21 (TGF-\u03b21) increased 4-fold in the oral mucosa. Surprisingly, blocking TGF-\u03b21 signaling with the TGF-R1 kinase inhibitor, LY364947, did not reduce Tc17 or Tc1 numbers. Nonetheless, LY364947 increased \u03b3\u03b4 T cell numbers and decreased CD49a expression on Tc1 cells. Although IL-17A-expressing \u03b3\u03b4 T cells were reduced by 30%, LC<jats:sup>\u0394MHC-II<\/jats:sup> mice displayed greater resistance to <jats:italic>Candida albicans<\/jats:italic> in early stages of oral infection. These findings suggest that modulating MHC-II expression in oral LC may be an effective strategy against fungal infections at mucosal surfaces counteracted by IL-17A-dependent mechanisms.<\/jats:p>","DOI":"10.3389\/froh.2024.1408255","type":"journal-article","created":{"date-parts":[[2024,5,30]],"date-time":"2024-05-30T10:07:06Z","timestamp":1717063626000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["MHC-II presentation by oral Langerhans cells impacts intraepithelial Tc17 abundance and Candida albicans oral infection via CD4 T cells"],"prefix":"10.3389","volume":"5","author":[{"given":"Peter D.","family":"Bittner-Eddy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lori A.","family":"Fischer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Praveen 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