AUTHOR=Bittner-Eddy Peter D. , Fischer Lori A. , Parachuru Praveen Venkata , Costalonga Massimo 

TITLE=MHC-II presentation by oral Langerhans cells impacts intraepithelial Tc17 abundance and Candida albicans oral infection via CD4 T cells

JOURNAL=Frontiers in Oral Health

VOLUME=Volume 5 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/oral-health/articles/10.3389/froh.2024.1408255

DOI=10.3389/froh.2024.1408255

ISSN=2673-4842

ABSTRACT=In a murine model (LC ΔMHC-II ) designed to abolish MHC-II expression in Langerhans cells (LCs), ~18% of oral LCs retain MHC-II, yet oral mucosal CD4 T cells numbers are unaffected.In LC ΔMHC-II mice, we now show that oral intraepithelial conventional CD8ab T cell numbers expand 30-fold. Antibody-mediated ablation of CD4 T cells in wild-type mice also resulted in CD8ab T cell expansion in the oral mucosa. Therefore, we hypothesize 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-g (Tc1 cells). These oral CD8 T cells showed broad T cell receptor Vb gene usage indicating responsiveness to diverse oral antigens. Generally supporting Tc17 cells, transforming growth factor -b1 (TGF-b1) increased 4-fold in the oral mucosa. Surprisingly, blocking TGF-b1 signaling with the TGF-R1 kinase inhibitor, LY364947, did not reduce Tc17 or Tc1 numbers. Nonetheless, LY364947 increased gd T cell numbers and decreased CD49a expression on Tc1 cells. Although IL-17A-expressing gd T cells were reduced by 30%, LC ΔMHC-II mice displayed greater resistance to Candida albicans 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.