title: IL-12 protects from psoriasiform skin inflammation.
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.
authors.affiliation: Institute of Experimental Immunology, University of Zurich, 8057 Zurich, Switzerland.
authors.forename: Paulina
authors.initials: P
authors.lastname: Kulig
authors.affiliation: Experimental Immunology Unit, Centre of Allergy and Environment (ZAUM), Technical University of Munich and Helmholtz Centre Munich, 80802 Munich, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Musiol
authors.affiliation: Department of Dermatology, University Hospital Zurich, 8091 Zurich, Switzerland.
authors.forename: Sandra Nicole
authors.initials: SN
authors.lastname: Freiberger
authors.affiliation: Institute of Experimental Immunology, University of Zurich, 8057 Zurich, Switzerland.
authors.forename: Bettina
authors.initials: B
authors.lastname: Schreiner
authors.affiliation: Institute for Research in Biomedicine, Cellular Immunology, 6500 Bellinzona, Switzerland.
authors.forename: Gabor
authors.initials: G
authors.lastname: Gyülveszi
authors.affiliation: Functional Genomics Center Zurich, University of Zurich and ETH Zurich, 8057 Zurich, Switzerland.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Russo
authors.affiliation: Institute of Experimental Immunology, University of Zurich, 8057 Zurich, Switzerland.
authors.forename: Stanislav
authors.initials: S
authors.lastname: Pantelyushin
authors.affiliation: Department of Immunology, Faculty of Pharmaceutical Sciences, Nagasaki International University, 859-3298 Nagasaki, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kishihara
authors.affiliation: Experimental Immunology Unit, Centre of Allergy and Environment (ZAUM), Technical University of Munich and Helmholtz Centre Munich, 80802 Munich, Germany.
authors.forename: Francesca
authors.initials: F
authors.lastname: Alessandrini
authors.affiliation: Department of Dermatology, University Hospital Zurich, 8091 Zurich, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kündig
authors.affiliation: Institute for Research in Biomedicine, Cellular Immunology, 6500 Bellinzona, Switzerland.
authors.forename: Federica
authors.initials: F
authors.lastname: Sallusto
authors.affiliation: Department of Dermatology, University Hospital Zurich, 8091 Zurich, Switzerland.
authors.forename: Günther F L
authors.initials: GF
authors.lastname: Hofbauer
authors.affiliation: Experimental Immunology Unit, Centre of Allergy and Environment (ZAUM), Technical University of Munich and Helmholtz Centre Munich, 80802 Munich, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Haak
authors.affiliation: Institute of Experimental Immunology, University of Zurich, 8057 Zurich, Switzerland.
authors.forename: Burkhard
authors.identifier: 0000-0002-1541-7867
authors.initials: B
authors.lastname: Becher
mesh_terms: D000634:Aminoquinolines / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D005260:Female; D006801:Humans; D000077271:Imiquimod; D007249:Inflammation / Q000150:complications / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*; D018664:Interleukin-12 / Q000378:metabolism*; D053759:Interleukin-23 / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008810:Mice, Inbred C57BL; D011565:Psoriasis / Q000150:complications / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000473:pathology*
chemical_list: D000634:Aminoquinolines; D053759:Interleukin-23; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018664:Interleukin-12; D000077271:Imiquimod