IL-12 protects from psoriasiform skin inflammation.

Autor: 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.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2016 Nov 28; Vol. 7, pp. 13466. Date of Electronic Publication: 2016 Nov 28.
DOI: 10.1038/ncomms13466
Abstrakt: 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.
Databáze: MEDLINE
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