IL-12 protects from psoriasiform skin inflammation.
Journal article

IL-12 protects from psoriasiform skin inflammation.

  • Kulig P Institute of Experimental Immunology, University of Zurich, 8057 Zurich, Switzerland.
  • Musiol S Experimental Immunology Unit, Centre of Allergy and Environment (ZAUM), Technical University of Munich and Helmholtz Centre Munich, 80802 Munich, Germany.
  • Freiberger SN Department of Dermatology, University Hospital Zurich, 8091 Zurich, Switzerland.
  • Schreiner B Institute of Experimental Immunology, University of Zurich, 8057 Zurich, Switzerland.
  • Gyülveszi G Institute for Research in Biomedicine, Cellular Immunology, 6500 Bellinzona, Switzerland.
  • Russo G Functional Genomics Center Zurich, University of Zurich and ETH Zurich, 8057 Zurich, Switzerland.
  • Pantelyushin S Institute of Experimental Immunology, University of Zurich, 8057 Zurich, Switzerland.
  • Kishihara K Department of Immunology, Faculty of Pharmaceutical Sciences, Nagasaki International University, 859-3298 Nagasaki, Japan.
  • Alessandrini F Experimental Immunology Unit, Centre of Allergy and Environment (ZAUM), Technical University of Munich and Helmholtz Centre Munich, 80802 Munich, Germany.
  • Kündig T Department of Dermatology, University Hospital Zurich, 8091 Zurich, Switzerland.
  • Sallusto F Institute for Research in Biomedicine, Cellular Immunology, 6500 Bellinzona, Switzerland.
  • Hofbauer GF Department of Dermatology, University Hospital Zurich, 8091 Zurich, Switzerland.
  • Haak S Experimental Immunology Unit, Centre of Allergy and Environment (ZAUM), Technical University of Munich and Helmholtz Centre Munich, 80802 Munich, Germany.
  • Becher B Institute of Experimental Immunology, University of Zurich, 8057 Zurich, Switzerland.
Show more…
  • 2016-11-29
Published in:
  • Nature communications. - 2016
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
  • English
Open access status
gold
Identifiers
Persistent URL
https://sonar.ch/global/documents/184211
Statistics

Document views: 12 File downloads: