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CD4 +Treg expansion arrests disease progression in a pre-clinical model of alopecia areata
Abstract   Peer reviewed

CD4 +Treg expansion arrests disease progression in a pre-clinical model of alopecia areata

Maddison Lensing, Samuel J Connell, Payton Kahl, Zhaowen Zhu and Ali Jabbari
The Journal of immunology (1950), Vol.210(1_Supplement), pp.165-165.09
05/01/2023
DOI: 10.4049/jimmunol.210.Supp.165.09

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Abstract

Abstract Alopecia Areata (AA) is a prevalent autoimmune disease that results in nonscarring hair loss. Disease is associated with the collapse of an immune privileged state of the hair follicle, characterized by increased MHC expression, immune cell infiltration and the presence of pro-inflammatory cytokines in the microenvironment. CD8 T cells have been identified as the main contributors to disease and the activating receptor NKG2D can identify this pathogenic population. There is currently one FDA-approved drug for AA, a JAK1/2 inhibitor, which is thought to act by dampening inflammatory mediators during disease. However, the potential of adverse effects and refractory patients necessitates the development of alternative therapeutics. Emerging data from our lab suggests that the observed expansion of CD4 T regulatory cells (Tregs), relative to effector CD8 T cells during AA, is inadequate to prevent disease onset. We hypothesized that pharmacologic enhancement of Treg numbers may restrain development of AA. To address this, we investigated the protective potential of Treg expansion using a murine model of AA. In vivo expansion of CD4 +CD25 +FoxP3 +Tregs was achieved using an IL-2 cytokine/antibody complex (IL-2C), which is known to selectively expand and enhance Tregs. We found that 6 weeks of treatment with IL-2C halted the progression of hair loss, while control mice exhibited robust hair loss. Additionally, IL-2C treatment led to a reduction in NKG2D +CD8 T cells and IFNγ-producing CD8 T cells found infiltrating the skin, suggesting that increasing Tregs in the system is an effective strategy for restraining disease. Our findings provide translational insight for the use of Treg enrichment as a therapeutic strategy for patients with AA. Supported by grants from NIH (R01 AR077194) and Dept. of VA (I01 BX004907)

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