Neutrophil Extracellular Traps Are Induced in a Psoriasis Model of Interleukin-36 Receptor Antagonist-deficient Mice

Overview

Journal Sci Rep

Specialty Science

Date 2020 Nov 20

PMID 33214582

Citations 11

Authors

Soichiro Watanabe

Yohei Iwata

Hidehiko Fukushima

Kenta Saito

Yoshihito Tanaka

Yurie Hasegawa

Masashi Akiyama

Kazumitsu Sugiura

Affiliations

Soon will be listed here.

Abstract

Loss-of-function mutations in the interleukin (IL)-36 gene IL36RN are associated with psoriasis. The importance of neutrophil extracellular traps (NETs), web-like structures composed of neutrophil DNA, in the pathogenesis of psoriasis has been unclear. Here, we aimed to clarify the role of NET signaling in the deficiency of IL36 receptor antagonist (DITRA). We evaluated the severity of psoriasis-like lesions induced by imiquimod cream treatment in Il36rn mice. The mRNA levels of psoriasis-related cytokines were measured via real-time reverse transcription polymerase chain reaction, and the effects of Cl-amidine, a peptidyl arginine deiminase 4 (PAD4) inhibitor, on psoriasis-like lesions were evaluated. PAD4 is a histone-modifying enzyme that is involved in NET formation. Psoriasis area and severity index scores, epidermal thickness, and infiltrated neutrophil counts were significantly increased in Il36rn mice; NET formation was confirmed pathologically. Several cytokines and chemokines were upregulated in the skin lesions of Il36rn mice and Cl-amidine treatment improved these psoriasis-like lesions. These results suggest that NET formation plays an important role in the pathology of psoriasis-like lesions in these mice and might represent a promising therapeutic target for DITRA.

Citing Articles

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