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...

Full description

Saved in:
Bibliographic Details
Published in:Journal of investigative dermatology Vol. 139; no. 1; p. 146
Main Authors: 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
Format: Journal Article
Language:English
Published: United States 01.01.2019
Subjects:
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
Online Access:Get more information
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
Bibliography: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