Kulig, Paulina Musiol, Stephanie Freiberger, Sandra Nicole Schreiner, Bettina Gyülveszi, Gabor Russo, Giancarlo Pantelyushin, Stanislav Kishihara, Kenji Alessandrini, Francesca Kündig, Thomas Sallusto, Federica Hofbauer, Günther F.L. Haak, Stefan Becher, Burkhard 2016-11-28 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 γδT (γδT17) 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. application/pdf https://localhost:5000/ark:/12658/srd1318988 https://susi.usi.ch/global/documents/318988 https://susi.usi.ch/documents/318988/files/Kulig_NC_2016.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1038/ncomms13466 info:eu-repo/semantics/altIdentifier/ark/12658/srd1318988 info:eu-repo/semantics/openAccess CC BY Nature communications. - 2016, vol. 7, p. 13466 Interleukins Psoriasis info:eu-repo/classification/udc/61 IL-12 protects from psoriasiform skin inflammation http://purl.org/coar/resource_type/c_6501