Aki Anri, Nagasaki Miyuki, Malynn Barbara Ann, Ma Averil, Kagari Takashi
Biologics & Immuno-Oncology Laboratories, Oncology Function, R&D Division, Daiichi Sankyo Co., Ltd., Tokyo, Japan.
Department of Medicine, University of California San Francisco, San Francisco, CA, United States of America.
PLoS One. 2017 Jun 28;12(6):e0180481. doi: 10.1371/journal.pone.0180481. eCollection 2017.
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.
银屑病是一种常见的炎症性皮肤病，全球约1%的人口受其影响。肿瘤坏死因子-α诱导蛋白3（TNFAIP3）基因多态性与银屑病易感性密切相关。在本研究中，我们探究了TNFAIP3（也称为A20）如何调节银屑病易感性。我们发现，与野生型小鼠相比，单倍体不足的A20+/-小鼠由于白细胞介素（IL）-17和IL-23产生增加，会发生严重的Toll样受体（TLR）诱导的皮肤炎症。对银屑病患者皮肤活检样本中TNFAIP3 mRNA表达的检测显示，在受累皮肤和未受累皮肤中其表达均降低。我们的结果证明了银屑病中A20在真皮层表达降低的临床重要性，并表明A20对IL-23/17轴的限制可预防银屑病。
