Host: The Japanese Pharmacological Society
Name : The 95th Annual Meeting of the Japanese Pharmacological Society
Number : 95
Location : Fukuoka
Date : March 07, 2022 - March 09, 2022
Atopic dermatitis (AD) is a chronic inflammatory skin disease affecting 7–15% of the general population in Japan. AD is characterized by recurrent eczematous legions and intense itch. As itch sensation induces scratching behavior, which exacerbates the skin inflammation and disturbs the quality of life of affected individuals, chronic itch is a challenging clinical problem in the treatment of AD. IL-31 is a major pruritogen associated with AD, and mainly produced by helper T cells. However, the mechanism for IL-31 production remained unknown.
Mutations of DOCK8 in humans cause a combined immunodeficiency characterized by AD. We have previously reported that DOCK8-deficient (Dock8–/–), but not Dock8+/–, mice spontaneously develop AD-like skin disease, when crossed with transgenic mice expressing AND T-cell receptor (TCR). Importantly, upon stimulation with cognate antigen, helper T cells from Dock8–/– AND Tg mice produce large amounts of IL-31 in a manner depending on the transcriptional factor EPAS1. Although EPAS1 is known to control hypoxic response through the interaction with arly hydrocarbon receptor nuclear translocator (ARNT), EPAS1-mediated IL31 promoter activation is independent of ARNT, but in collaboration with SP1. Therefore, EPAS1–SP1 axis could be a drug target for treatment of AD-associated itch. In my talk, I will discuss the molecular basis for IL-31 production in helper T cells, referring to its application to drug development.
