The molecular basis for IL-31 production and IL-31-mediated itch transmission: from biology to drug development. (7th September 2021)

• Record Type: Journal Article
• Authors: Kunimura, Kazufumi; Fukui, Yoshinori
• Is Part Of: International immunology. Volume 33:Number 12(2021)
• Page Start: 731
• Page End: 736
• Publication Date: 2021-09-07
• Subjects: atopic dermatitis -- chemical compounds -- EPAS1 -- neurokinin B -- SP1; Immunology -- Periodicals; 616.079
• DOI: 10.1093/intimm/dxab065
• Languages: English
• ISSNs: 0953-8178

Abstract

Abstract: Atopic dermatitis (AD) is one of the most prevalent chronic inflammatory skin diseases in the world. It is characterized by recurrent eczematous lesions and intense itch, and many cytokines are involved in the pathogenesis of AD. Among them, much attention has been paid to interleukin 31 (IL-31) as an AD-associated itch mediator. IL-31 is mainly produced by CD4 + helper T cells and transmits the signals via a heterodimeric receptor composed of IL-31 receptor A (IL-31RA) and oncostatin M receptor (OSMR), both of which are expressed in dorsal root ganglion (DRG) neurons. However, the molecular mechanisms of how IL-31 is produced in helper T cells upon stimulation and transmits the itch sensation to the brain were largely unknown. Recently, by using original mouse models of AD, we have identified endothelial PAS domain 1 (EPAS1) and neurokinin B (NKB) as key molecules critical for IL-31 production and IL-31-mediated itch transmission, respectively. These molecules could be novel drug targets for AD-associated itch. This review highlights our recent findings, which show the functional significance of these molecules in the IL-31-induced itch sensation, referring to their application to drug development.