Interleukin-17 receptor A (IL-17RA) is a key regulator of type 2 inflammatory responses involved in maintaining immune system homeostasis. (IRC7P.431)

Abstract

Abstract IL-17 cytokine family signaling is a key mediator of skin inflammatory disorders including atopic dermatitis and psoriasis. It has previously been shown that deficiency of IL-17 producing cells and especially TCRγδ T cells attenuates the skin inflammatory phenotype observed in murine models of psoriasis. Mice lacking IL-17 receptor A expression, through which IL-17A and other IL-17 family cytokines signal, develop severe and progressive skin inflammation. This spontaneous skin inflammation was characterized by increased epidermal thickness with cellular infiltration, which was accompanied with lymphadenopathy, and type 2 responses, including eosinophilia and increased serum levels of IgE. On a cellular level a significant increase in the numbers of innate lymphoid cell subpopulations was observed. Additionally IL-17RA-/- mice have increased γδ T cells with an activated memory-like phenotype. To further elucidate the role of IL-17 family cytokines in atopic dermatitis (AD) we crossed IL-17RA-/- mice with mice, carrying a mutation previously associated with human AD, that results in a spontaneous atopic dermatitis-like disease. The absence of IL-17RA signaling resulted in a severely accelerated AD like inflammation. This highlights that IL-17RA signaling is required for maintaining homeostasis including the regulation of Th2 responses.