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
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    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.
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  • English
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Medicine
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https://susi.usi.ch/usi/documents/318988
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