AUTHOR=Akazawa Hiroki , Nozaki Yuji , Yamazawa Hirotaka , Ishimura Kaori , Ashida Chisato , Okada Akinori , Kinoshita Koji , Matsumura Itaru 

TITLE=Blockade of IL-18Rα-mediated signaling pathway exacerbates neutrophil infiltration in imiquimod-induced psoriasis murine model

JOURNAL=Frontiers in Medicine

VOLUME=10

YEAR=2023

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2023.1293132

DOI=10.3389/fmed.2023.1293132

ISSN=2296-858X

ABSTRACT=<p>Psoriasis is an immune-mediated inflammatory disease of the skin, which is characterized by epidermal hyperkeratosis and neutrophil infiltration. The interleukin (IL)-17/IL-23 pathway and associated cytokines play major roles in the pathogenesis and exacerbation of psoriasis. The IL-18/IL-18 receptor (R) α signaling pathway is important for Th1 cytokine production and differentiation of Th1 cells; however, its role in the pathogenesis of psoriasis remains unknown. In this study, we investigated the effect of the IL-18Rα-mediated signaling pathway in the pathogenesis of psoriasis in <italic>Il18ra-</italic>deficient mice (<italic>Il18ra</italic><sup><bold>−</bold>/<bold>−</bold></sup>) and wild-type imiquimod (IMQ)-induced psoriatic dermatitis model mice. Blocking this pathway exacerbated IMQ-induced psoriatic skin inflammation. <italic>Il18ra</italic> deficiency led to significant increases in the levels of IL-1β, IL-6, IL-8, IL-17A, IL-23, and chemokine (C-X-C motif) ligand 2 in skin lesions. Gr1-positive cells highly infiltrated psoriatic skin lesions in <italic>Il18ra</italic><sup><bold>−</bold>/<bold>−</bold></sup> mice compared to those in wild-type mice. Citrullinated histone H3-positive area was relatively broad in <italic>Il18ra</italic><sup><bold>−</bold>/<bold>−</bold></sup> mice. These results suggest that IL-18Rα-mediated signaling pathways may inhibit psoriatic skin inflammation by regulating infiltration and activation of neutrophil and other innate immune cells.</p>