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
-
- English
- Classification
- Medicine
- License
- License undefined
- Identifiers
-
- RERO DOC 326998
- DOI 10.1038/ncomms13466
- ARK ark:/12658/srd1318988
- Persistent URL
- https://n2t.net/ark:/12658/srd1318988
Statistics
Document views: 41
File downloads:
- Kulig_NC_2016.pdf: 45