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

Frontiers in Medicine

Medicine

Chisato Ashida¹  Kaori Ishimura¹  Koji Kinoshita¹  Hirotaka Yamazawa¹  Akinori Okada¹  Itaru Matsumura¹  Hiroki Akazawa²  Yuji Nozaki² 

[1] Department of Hematology and Rheumatology, Kindai University Faculty of Medicine, Osakasayama, Japan;null;

关键词: immune-mediated inflammatory disease;    psoriasis;    IL-18Rα;    neutrophil;    innate immunity;   

DOI  :  10.3389/fmed.2023.1293132

 received in 2023-09-25, accepted in 2023-10-16,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

Unknown   
Copyright © 2023 Akazawa, Nozaki, Yamazawa, Ishimura, Ashida, Okada, Kinoshita and Matsumura.