Research Article: Hypomorphic A20 expression confers susceptibility to psoriasis

Date Published: June 28, 2017

Publisher: Public Library of Science

Author(s): Anri Aki, Miyuki Nagasaki, Barbara Ann Malynn, Averil Ma, Takashi Kagari, Edward William Harhaj.

http://doi.org/10.1371/journal.pone.0180481

Abstract

Psoriasis is a common inflammatory skin disease that affects approximately 1% of the population worldwide. Tumor necrosis factor-alpha-induced protein 3 (TNFAIP3) gene polymorphisms have been strongly associated with psoriasis susceptibility. In this study, we investigate how TNFAIP3, also known as A20, may regulate psoriasis susceptibility. We found that haplo-insufficient A20+/- mice develop severe toll-like receptor (TLR)-induced skin inflammation compared to wild type mice owing to amplified production of interleukin (IL)-17 and IL-23. Examination of TNFAIP3 mRNA expression in skin biopsies from patients with psoriasis revealed reduced expression in both involved and uninvolved skin. Our results demonstrate the clinical importance of reduced dermal expression of A20 in psoriasis and suggest that A20 restriction of the IL-23/17 axis protects against psoriasis.

Partial Text

Psoriasis is a common immune-mediated skin disease that is caused by complex factors including the environment and genetic background. Recently, a genome wide association study of psoriasis cases revealed susceptibility loci with confirmed association to the disease, including human leukocyte antigen (HLA)-C, three genes involved in IL-23 signaling (IL23A, IL23R, IL12B), two genes acting downstream of tumor necrosis factor-alpha (TNFα) and regulating nuclear factor-kappa B (NF-κB) signaling (TNIP1, TNFAIP3), and two genes involved in the modulation of T helper 2 (Th2) immune responses (IL4, IL13) [1]. These results implicate these three pathways in psoriasis pathogenesis and suggest that genetic susceptibility could partially explain heterogeneity in treatment responses to TNFα blockade among patients with psoriasis. In this regard, a recent report showed that TNFAIP3 gene single nucleotide polymorphisms (SNPs) were associated with response to TNFα blockade in psoriasis [2].

 

Source:

http://doi.org/10.1371/journal.pone.0180481

 

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