TY - JOUR
T1 - The molecular basis for IL-31 production and IL-31-mediated itch transmission
T2 - From biology to drug development
AU - Kunimura, Kazufumi
AU - Fukui, Yoshinori
N1 - Funding Information:
This work was supported by Leading Advanced Projects for Medical Innovation (grant no. JP19gm0010001) and Advanced Research and Development Programs for Medical Innovation (grant no. JP20gm1310005) from Japan Agency for Medical Research and Development (to Y.F.)
Publisher Copyright:
© 2021 The Author(s) 2021. Published by Oxford University Press on behalf of The Japanese Society for Immunology.
PY - 2021/12/1
Y1 - 2021/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85121249798&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85121249798&partnerID=8YFLogxK
U2 - 10.1093/intimm/dxab065
DO - 10.1093/intimm/dxab065
M3 - Review article
C2 - 34491348
AN - SCOPUS:85121249798
VL - 33
SP - 731
EP - 736
JO - International Immunology
JF - International Immunology
SN - 0953-8178
IS - 12
ER -