TWEAK Mediates Inflammation in Experimental Atopic Dermatitis and Psoriasis

Overview

Journal Nat Commun

Specialty Biology

Date 2017 May 23

PMID 28530223

Citations 30

Authors

Daniel Sidler

Ping Wu

Rana Herro

Meike Claus

Dennis Wolf

Yuko Kawakami

Toshiaki Kawakami

Linda Burkly

Michael Croft

Affiliations

Soon will be listed here.

Abstract

Atopic dermatitis (AD) and psoriasis are driven by alternate type 2 and type 17 immune responses, but some proteins might be critical to both diseases. Here we show that a deficiency of the TNF superfamily molecule TWEAK (TNFSF12) in mice results in defective maintenance of AD-specific T helper type 2 (Th2) and psoriasis-specific Th17 cells in the skin, and impaired expression of disease-characteristic chemokines and cytokines, such as CCL17 and TSLP in AD, and CCL20 and IL-19 in psoriasis. The TWEAK receptor, Fn14, is upregulated in keratinocytes and dermal fibroblasts, and TWEAK induces these cytokines and chemokines alone and in synergy with the signature T helper cytokines of either disease, IL-13 and IL-17. Furthermore, subcutaneous injection of recombinant TWEAK into naive mice induces cutaneous inflammation with histological and molecular signs of both diseases. TWEAK is therefore a critical contributor to skin inflammation and a possible therapeutic target in AD and psoriasis.

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