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039 Expansion of regulatory T Cells restrains pathogenic CD8 T Cells in a murine model of alopecia areata
Abstract   Peer reviewed

039 Expansion of regulatory T Cells restrains pathogenic CD8 T Cells in a murine model of alopecia areata

M. Lensing, S.J. Connell, P. Kahl, Z. Zhu, O. Ayush and A. Jabbari
Journal of investigative dermatology, Vol.144(8 Supplement), pp.S7-S7
08/2024
DOI: 10.1016/j.jid.2024.06.055

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Abstract

Alopecia Areata (AA) is a prevalent autoimmune disease that causes nonscarring hair loss. Disease is associated with a collapse of immune privilege of the hair follicle, which is characterized by increased MHC expression, immune cell infiltration and pro-inflammatory cytokines around and within the hair follicle. NKG2D-expressing CD8 T cells have been identified as primary disease effectors (Teff). Current FDA-approved treatments for AA are limited to two JAK inhibitors, which are thought to act by stifling inflammatory mediators during disease. However, potential adverse effects and refractory patients necessitates the development of alternative therapeutic strategies. Our lab has observed that the expansion of CD4 T regulatory cells (Tregs) is inadequate to prevent disease onset, with Teff outnumbering Tregs 32-fold in diseased skin. We hypothesized that pharmacologic enhancement of Treg numbers may restrain development of AA. Using a skin-graft induction model of AA, our objective was to assess preventative and therapeutic efficacy of in vivo Treg expansion by treating mice with an IL-2 cytokine/antibody complex. Treg expansion prevented the onset of AA and was accompanied by skewing the ratio of Tregs: Teff in the skin to favor Tregs (12-fold higher than Teff). Therapeutic Treg expansion arrested the progression of disease development, which was marked by arrest of hair loss. IL-2C treatment led to a significant reduction in NKG2D+ CD8 T cells (p = 0.0013) and IFNg-producing CD8 T cells (p =0.0007) found infiltrating the skin, suggesting that increasing Tregs is an effective strategy for restraining disease. Interestingly, combining Treg expansion with a systemic corticosteroid prolonged the durability of this protective effect after treatment discontinuation. Overall, our findings provide translational insight for the use of Treg enrichment as a therapeutic strategy for patients with AA.

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