Exogenous IL-27 prevents the development of alopecia areata

Abstract Alopecia areata (AA) is an autoimmune disease with a 2% lifetime incidence. Commonly presenting as defined patches of hair loss on the scalp, AA is characterized by the presence of T cells surrounding the hair bulb and is thought to result as a consequence of the breakdown of immune privilege of the hair follicle. IL-27 is a cytokine with context-dependent pro- and anti-inflammatory properties that has been used as a potential therapy in models of autoimmune diseases and cancer. The objective of this study was to determine if IL-27 has therapeutic potential in AA. To address this, we used an adeno-associated virus that drives the overexpression of IL-27 (AAV-IL27) in our skin-graft induction model of AA. We found that mice that received AAV-IL27 were fully protected from disease development and had minimal CD8 T cell infiltration into the hair follicles. Further, we saw an increase in IL-10 producing CD4 T cells, supporting a potential mechanism by which IL-27 prevents disease development. Interestingly, we found that mice treated with AAV-IL27 generated a robust population of NKG2D expressing CD8 T cells, which has previously been associated with the presence of disease. These results suggest that IL-27 may act in an immunoregulatory manner in AA, by promoting immunosuppressive T cells in the SDLNs. Further studies are needed to further define the specific mechanisms by which IL-27 contributes to the prevention of AA and its utility as a treatment for AA.