IL-12 protects from psoriasiform skin inflammation

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

doi:10.1038/ncomms13466

Back

Journal article

IL-12 protects from psoriasiform skin inflammation

Kulig, Paulina Institute of Experimental Immunology, University of Zurich, 8057 Zurich, Switzerland
Musiol, Stephanie Experimental Immunology Unit, Centre of Allergy and Environment (ZAUM), Technical University of Munich and Helmholtz Centre Munich, 80802 Munich, Germany
Freiberger, Sandra Nicole Department of Dermatology, University Hospital Zurich, 8091 Zurich, Switzerland
Schreiner, Bettina Institute of Experimental Immunology, University of Zurich, 8057 Zurich, Switzerland
Gyülveszi, Gabor Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Russo, Giancarlo Functional Genomics Center Zurich, University of Zurich and ETH Zurich, 8057 Zurich, Switzerland
Pantelyushin, Stanislav Institute of Experimental Immunology, University of Zurich, 8057 Zurich, Switzerland
Kishihara, Kenji Department of Immunology, Faculty of Pharmaceutical Sciences, Nagasaki International University, 859-3298 Nagasaki, Japan
Alessandrini, Francesca Experimental Immunology Unit, Centre of Allergy and Environment (ZAUM), Technical University of Munich and Helmholtz Centre Munich, 80802 Munich, Germany
Kündig, Thomas Department of Dermatology, University Hospital Zurich, 8091 Zurich, Switzerland
Sallusto, Federica Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Hofbauer, Günther F.L. Department of Dermatology, University Hospital Zurich, 8091 Zurich, Switzerland
Haak, Stefan Experimental Immunology Unit, Centre of Allergy and Environment (ZAUM), Technical University of Munich and Helmholtz Centre Munich, 80802 Munich, Germany
Becher, Burkhard Institute of Experimental Immunology, University of Zurich, 8057 Zurich, Switzerland

28.11.2016

Published in:

Nature communications. - 2016, vol. 7, p. 13466

English 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.

Language