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

ABSTRACT: 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-1? 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 ?? T cells and other cells such as keratinocytes is essential to an IMQ-induced skin inflammation. IL-1? induces dermal ?? T cell proliferation and IL-17 production in mice. In addition, IL-1? stimulates keratinocytes to secrete chemokines that preferentially chemoattract peripheral CD27- CCR6+IL-17 capable of producing ?? T cells (??T17). Further studies showed that endogenous IL-1? secretion is regulated by skin commensals to maintain dermal ??T17 homeostasis in mice. Mouse skin associated with Corynebacterium species, bacteria enriched in human psoriatic lesional skin, has increased IL-1? and dermal ??T17 cell expansion. Thus, the IL-1?-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.

SUBMITTER: Cai Y 

PROVIDER: S-EPMC6392027 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature