| First Author | Kulig P | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 13466 | PubMed ID | 27892456 |
| Mgi Jnum | J:243059 | Mgi Id | MGI:5907551 |
| Doi | 10.1038/ncomms13466 | Citation | Kulig P, et al. (2016) IL-12 protects from psoriasiform skin inflammation. Nat Commun 7:13466 |
| abstractText | Neutralization of the common p40-subunit of IL-12/23 in psoriasis patients has led to a breakthrough in the management of moderate to severe disease. Aside from neutralizing IL-23, which is thought to be responsible for the curative effect, anti-p40 therapy also interferes with IL-12 signalling and type 1 immunity. Here we dissect the individual contribution of these two cytokines to the formation of psoriatic lesions and understand the effect of therapeutic co-targeting of IL-12 and IL-23 in psoriasis. Using a preclinical model for psoriatic plaque formation we show that IL-12, in contrast to IL-23, has a regulatory function by restraining the invasion of an IL-17-committed gammadeltaT (gammadeltaT17) cell subset. We discover that IL-12 receptor signalling in keratinocytes initiates a protective transcriptional programme that limits skin inflammation, suggesting that collateral targeting of IL-12 by anti-p40 monoclonal antibodies is counterproductive in the therapy of psoriasis. |
