A Critical Role of the IL-1β-IL-1R Signaling Pathway in Skin Inflammation and Psoriasis Pathogenesis

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 les...

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Vydáno v:	Journal of investigative dermatology Ročník 139; číslo 1; s. 146
Hlavní autoři:	Cai, Yihua, Xue, Feng, Quan, Chen, Qu, Minye, Liu, Na, Zhang, Yuan, Fleming, Chris, Hu, Xiaoling, Zhang, Huang-Ge, Weichselbaum, Ralph, Fu, Yang-Xin, Tieri, David, Rouchka, Eric C, Zheng, Jie, Yan, Jun
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States 01.01.2019
Témata:	Animals Cell Proliferation Enzyme-Linked Immunosorbent Assay Gene Expression Regulation Humans Inflammation - genetics Inflammation - metabolism Inflammation - pathology Interleukin-1beta - blood Interleukin-1beta - genetics Keratinocytes - metabolism Keratinocytes - pathology Mice Mice, Knockout Polymerase Chain Reaction Psoriasis - genetics Psoriasis - metabolism Psoriasis - pathology Receptors, Interleukin-1 Type I - biosynthesis Receptors, Interleukin-1 Type I - genetics RNA - genetics
ISSN:	1523-1747, 1523-1747
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Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1523-1747 1523-1747
DOI:	10.1016/j.jid.2018.07.025