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. Il36r ΔK 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.
Highlights
Psoriasis is a chronic inflammatory disease which affects around 1–2% of the world’s population
A causative mutation of IL-36Ra has been associated with generalized pustular psoriasis (GPP) (Marrakchi et al, 2011; Onoufriadis et al, 2011) and treatment with a monoclonal antibody targeting IL-36 receptor (IL-36R) showed clinical efficiency in seven GPP patients (Bachelez et al, 2019)
IL-36R–deficient mice are protected against Aldara-induced psoriasis-like dermatitis, and expression of IL-36R in radio-resistant cells is critical for the pathogenesis (Tortola et al, 2012)
Summary
Psoriasis is a chronic inflammatory disease which affects around 1–2% of the world’s population It is characterized by epidermal hyperplasia (acanthosis), formation of erythematous plaques, dermo-epidermal inflammation, and angiogenesis. These manifestations are caused by infiltration of neutrophils and inflammatory mononuclear cells in the dermis and epidermis (Lowes et al, 2014; Boehncke & Schon, 2015). IL-36 stimulation promotes the release of chemokines and pro-inflammatory cytokines involved in psoriasis pathogenesis, notably in recruitment of neutrophils, and interferes with the processes of differentiation and cornification (Foster et al, 2014; Li et al, 2014; Bridgewood et al, 2017; Scheibe et al, 2017)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
