Alopecia areata (AA) is an autoimmune skin disease affecting the hair follicle. Alterations in the gut microbiome composition were previously reported in patients with AA, however the role of the gut microbiome in AA remains elusive. We found that germ-free C3H/HeJ mice, as well as specific pathogen-free C3H/HeJ mice treated with broad-spectrum antibiotics, were protected from AA. Accordingly, a significant gut dysbiosis characterized by an overrepresentation of Ligilactobacillus murinus and its metabolite lactic acid, preceded AA development in C3H/HeJ mice; while their depletion using a high-salt diet, delayed disease onset. Mechanistically, we identified that depletion of the gut microbiome abrogated priming of pathogenic NKG2D+CD8+ T cells in the skin, as well as the recruitment of CD40+ arginase 1 (Arg1) expressing monocyte-derived dendritic cells into the skin. Accordingly, blocking CD40/CD40L interaction or the Arg1 pathway prevented AA development. Consistent with our findings in the C3H/HeJ mice, human patients with AA exhibited a distinct shift in the relative abundance of bacterial species and showed a significant overrepresentation of Ligilactobacillus species in the gut. Herein, we identified gut dysbiosis in murine and human AA, and defined two novel mechanisms by which gut microbiome dysbiosis contributes to the pathogenesis of AA. Altogether, these findings invite new therapeutic approaches for the treatment of AA by targeting the gut microbiome.
Gut microbiome is required for priming of CD8+ NKG2D+ T cells in alopecia areata
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Poster and Podium (Block Symposium)
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Date: May 6 Presentation Time: 02:15 PM to 03:30 PM Room: Exhibit Hall F1