IL-12 protects from psoriasiform skin inflammation

Paulina Kulig, Stephanie Musiol, Sandra Nicole Freiberger, Bettina Schreiner, Gabor Gyülveszi, Giancarlo Russo, Stanislav Pantelyushin, Kenji Kishihara, Francesca Alessandrini, Thomas Kündig, Federica Sallusto, Günther F.L. Hofbauer, Stefan Haak () and Burkhard Becher ()
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Paulina Kulig: Institute of Experimental Immunology, University of Zurich
Stephanie Musiol: Experimental Immunology Unit, Centre of Allergy and Environment (ZAUM), Technical University of Munich and Helmholtz Centre Munich
Sandra Nicole Freiberger: University Hospital Zurich
Bettina Schreiner: Institute of Experimental Immunology, University of Zurich
Gabor Gyülveszi: Institute for Research in Biomedicine, Cellular Immunology
Giancarlo Russo: Functional Genomics Center Zurich, University of Zurich and ETH Zurich
Stanislav Pantelyushin: Institute of Experimental Immunology, University of Zurich
Kenji Kishihara: Faculty of Pharmaceutical Sciences, Nagasaki International University
Francesca Alessandrini: Experimental Immunology Unit, Centre of Allergy and Environment (ZAUM), Technical University of Munich and Helmholtz Centre Munich
Thomas Kündig: University Hospital Zurich
Federica Sallusto: Institute for Research in Biomedicine, Cellular Immunology
Günther F.L. Hofbauer: University Hospital Zurich
Stefan Haak: Experimental Immunology Unit, Centre of Allergy and Environment (ZAUM), Technical University of Munich and Helmholtz Centre Munich
Burkhard Becher: Institute of Experimental Immunology, University of Zurich

Nature Communications, 2016, vol. 7, issue 1, 1-14

Abstract: Abstract 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.

Date: 2016
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DOI: 10.1038/ncomms13466

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