TY - JOUR
T1 - A Critical Role of the IL-1β–IL-1R Signaling Pathway in Skin Inflammation and Psoriasis Pathogenesis
AU - Cai, Yihua
AU - Xue, Feng
AU - Quan, Chen
AU - Qu, Minye
AU - Liu, Na
AU - Zhang, Yuan
AU - Fleming, Chris
AU - Hu, Xiaoling
AU - Zhang, Huang ge
AU - Weichselbaum, Ralph
AU - Fu, Yang-Xin
AU - Tieri, David
AU - Rouchka, Eric C.
AU - Zheng, Jie
AU - Yan, Jun
N1 - Funding Information:
This work was supported by the National Institutes of Health R01AI128818 and the National Psoriasis Foundation (JY) and by the NSFC 81761128008 and 91442123 (JZ). Bioinformatics support for this work was provided by the National Institutes of Health grant P20GM103436 . HGZ is supported by a Research Career Scientist (RCA) Award.
Publisher Copyright:
© 2018 The Authors
PY - 2019/1
Y1 - 2019/1
N2 - The IL-1 signaling pathway has been shown to play a critical role in the pathogenesis of chronic, autoinflammatory skin diseases such as psoriasis. However, the exact cellular and molecular mechanisms have not been fully understood. Here, we show that IL-1β is significantly elevated in psoriatic lesional skin and imiquimod-treated mouse skin. In addition, IL-1R signaling appears to correlate with psoriasis disease progression and treatment response. IL-1 signaling in both dermal γδ T cells and other cells such as keratinocytes is essential to an IMQ-induced skin inflammation. IL-1β induces dermal γδ T cell proliferation and IL-17 production in mice. In addition, IL-1β stimulates keratinocytes to secrete chemokines that preferentially chemoattract peripheral CD27– CCR6+IL-17 capable of producing γδ T cells (γδT17). Further studies showed that endogenous IL-1β secretion is regulated by skin commensals to maintain dermal γδT17 homeostasis in mice. Mouse skin associated with Corynebacterium species, bacteria enriched in human psoriatic lesional skin, has increased IL-1β and dermal γδT17 cell expansion. Thus, the IL-1β–IL-1R signaling pathway may contribute to skin inflammation and psoriasis pathogenesis via the direct regulation of dermal IL-17–producing cells and stimulation of keratinocytes for amplifying inflammatory cascade.
AB - The IL-1 signaling pathway has been shown to play a critical role in the pathogenesis of chronic, autoinflammatory skin diseases such as psoriasis. However, the exact cellular and molecular mechanisms have not been fully understood. Here, we show that IL-1β is significantly elevated in psoriatic lesional skin and imiquimod-treated mouse skin. In addition, IL-1R signaling appears to correlate with psoriasis disease progression and treatment response. IL-1 signaling in both dermal γδ T cells and other cells such as keratinocytes is essential to an IMQ-induced skin inflammation. IL-1β induces dermal γδ T cell proliferation and IL-17 production in mice. In addition, IL-1β stimulates keratinocytes to secrete chemokines that preferentially chemoattract peripheral CD27– CCR6+IL-17 capable of producing γδ T cells (γδT17). Further studies showed that endogenous IL-1β secretion is regulated by skin commensals to maintain dermal γδT17 homeostasis in mice. Mouse skin associated with Corynebacterium species, bacteria enriched in human psoriatic lesional skin, has increased IL-1β and dermal γδT17 cell expansion. Thus, the IL-1β–IL-1R signaling pathway may contribute to skin inflammation and psoriasis pathogenesis via the direct regulation of dermal IL-17–producing cells and stimulation of keratinocytes for amplifying inflammatory cascade.
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U2 - 10.1016/j.jid.2018.07.025
DO - 10.1016/j.jid.2018.07.025
M3 - Article
C2 - 30120937
AN - SCOPUS:85055580402
VL - 139
SP - 146
EP - 156
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
IS - 1
ER -