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 - 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
SN - 0022-202X
VL - 139
SP - 146
EP - 156
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 1
ER -