IL-27 generates immunosuppressive CD4 T cells and and prevents the development of alopecia areata

Summary: Abstract Body: Alopecia areata (AA) is a T cell-mediated autoimmune disease of the hair follicle (HF) that presents as non-scarring hair loss and has a 2% lifetime incidence. AA is thought to occur from the breakdown of immune privilege of the HF resulting in infiltration of NKG2D-expressing CD8 T cells and attack of the HF. Recently, JAK inhibitors have been approved by the FDA for the treatment of AA, however, they have shown incomplete efficacy in clinical trials and have been associated with increased risk of catastrophic adverse events, thus supporting the need to find additional therapeutic options. IL-27 is a pleiotropic cytokine with context-dependent pro- and anti-inflammatory properties that has been investigated as a therapeutic option in models of autoimmunity and cancer. The aim of our study was to determine if IL-27 affected AA pathogenesis. We used an adeno-associated virus that drives expression of IL-27 (AAV-IL27) in the skin-graft induction model of AA and found that AAV-IL27 treatment protected mice from developing AA. In mice that were protected from AA, we saw an increase in IL-10 producing FoxP3-CD4+ T cells in the skin draining lymph nodes (SDLNs). Additionally, in mice that were treated with AAV-IL27, we observed a 1.3-fold decrease in CD127 expression in SDLN CD8 T cells, and a marked decrease in expression in skin CD8 T cells. Together these data suggest that IL-27 can lead to an increase in immunosuppressive CD4 T cells and diminished CD8 T cell responsiveness to IL-7, a cytokine pathway previously implicated in AA pathogenesis. Further studies are needed to examine the mechanisms by which IL-27 contributes to the prevention of disease and its utility as a therapy for AA. Samuel J. Connell¹, Payton Kahl¹, Zhaowen Zhu¹, Sydney Crotts¹, Maddison Lensing¹, Otgonzaya Ayush¹, Cristina Dix¹, Xue-Feng Bai², Ali Jabbari¹ 1. Dermatology, University of Iowa Health Care, Iowa City, IA, United States. 2. The Ohio State University, Columbus, OH, United States. Adaptive and Auto-Immunity