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

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

doi:10.3389/fmed.2023.1293132

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

Front Med (Lausanne). 2023 Oct 27:10:1293132. doi: 10.3389/fmed.2023.1293132. eCollection 2023.

Authors

Hiroki Akazawa¹, Yuji Nozaki¹, Hirotaka Yamazawa¹, Kaori Ishimura¹, Chisato Ashida¹, Akinori Okada¹, Koji Kinoshita¹, Itaru Matsumura¹

Affiliation

¹ Department of Hematology and Rheumatology, Kindai University Faculty of Medicine, Osakasayama, Japan.

Abstract

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 Il18ra-deficient mice (Il18ra^-/-) and wild-type imiquimod (IMQ)-induced psoriatic dermatitis model mice. Blocking this pathway exacerbated IMQ-induced psoriatic skin inflammation. Il18ra 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 Il18ra^-/- mice compared to those in wild-type mice. Citrullinated histone H3-positive area was relatively broad in Il18ra^-/- 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.

Keywords: IL-18Rα; immune-mediated inflammatory disease; innate immunity; neutrophil; psoriasis.