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

Yihua Cai, Feng Xue, Chen Quan, Minye Qu, Na Liu, Yuan Zhang, Chris Fleming, Xiaoling Hu, Huang ge Zhang, Ralph Weichselbaum, Yang-Xin Fu, David Tieri, Eric C. Rouchka, Jie Zheng, Jun Yan

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6 Scopus citations

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-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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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Cai, Y., Xue, F., Quan, C., Qu, M., Liu, N., Zhang, Y., Fleming, C., Hu, X., Zhang, H. G., Weichselbaum, R., Fu, Y-X., Tieri, D., Rouchka, E. C., Zheng, J., & Yan, J. (Accepted/In press). A Critical Role of the IL-1β–IL-1R Signaling Pathway in Skin Inflammation and Psoriasis Pathogenesis. Journal of Investigative Dermatology. https://doi.org/10.1016/j.jid.2018.07.025