IL-36 signaling in keratinocytes controls early IL-23 production in psoriasis-like dermatitis
Open Access
- 28 April 2020
- journal article
- research article
- Published by Life Science Alliance, LLC in Life Science Alliance
- Vol. 3 (6), e202000688
- https://doi.org/10.26508/lsa.202000688
Abstract
IL-36R signaling plays an important role in the pathogenesis of psoriasis. We ought to assess the specific function of IL-36R in keratinocytes for the pathology of Aldara-induced psoriasis-like dermatitis. Il36rΔK mice presenting deletion of IL-36R in keratinocytes were similarly resistant to Aldara-induced ear inflammation as Il36r−/− mice, but acanthosis was only prevented in Il36r−/− mice. FACS analysis revealed that IL-36R signaling in keratinocytes is mandatory for early neutrophil infiltration in Aldara-treated ears. RNASeq and qRT-PCR experiments demonstrated the crucial role of IL-36R signaling in keratinocytes for induction of IL-23, IL-17, and IL-22 at early time points. Taken together, our results demonstrate that IL-36R signaling in keratinocytes plays a major role in the induction of Aldara-induced psoriasis-like dermatitis by triggering early production of IL-23/IL-17/IL-22 cytokines and neutrophil infiltration.Funding Information
- Swiss National Science Foundation (310030_712674)
- Rheumasearch Foundation
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