| First Author | Sidler D | Year | 2017 |
| Journal | Nat Commun | Volume | 8 |
| Pages | 15395 | PubMed ID | 28530223 |
| Mgi Jnum | J:250594 | Mgi Id | MGI:5920365 |
| Doi | 10.1038/ncomms15395 | Citation | Sidler D, et al. (2017) TWEAK mediates inflammation in experimental atopic dermatitis and psoriasis. Nat Commun 8:15395 |
| abstractText | 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. |
