The emergence of Alopecia Areata is not dependent on perforin-mediated cytolysis

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B759
Abstract ID: 5159

Presenting Author:
Maddison Lensing , Graduate Research Assistant at Univ. of Iowa

Abstract:

Alopecia Areata (AA) is a prevalent autoimmune disease that presents as nonscarring hair loss. AA is associated with the loss of immune tolerance to the hair follicle and marked by a robust immune cell infiltration and production of pro-inflammatory cytokines. In AA, CD8 T cells accumulate around and within the hair follicle and have been identified as pathogenic effectors of disease. The close spatial relationship between cytotoxic CD8 T cells and the hair follicle end-organ target invites further study of the interactions between them. Our transcriptional analysis has revealed CD8 T cells infiltrating AA skin exhibit increased gene expression of perforin and granzymes, which are key mediators of cytolysis. However, the contributions of these cytolytic molecules in AA are currently unknown. Our objective was to investigate the role of perforin in the onset of AA by using C3H/HeJ mice globally deficient in Prf1 (PKO). Interestingly, PKO mice were capable of developing spontaneous AA. Using a skin-graft induction model, we observed that wild type (WT) and PKO recipient mice showed equivalent onset and progression of AA. However, when a CD8-induction model was used, we found CD8 T cells from PKO AA mice were inferior at inducing disease when compared to CD8 T cells from WT AA mice. Overall, our findings suggest that perforin-mediated cytolysis is not required for the autoimmune attack of the hair follicle, and that other effector mechanisms of CD8 T cells are drivers of AA.