title: Role of Tyk-2 in Th9 and Th17 cells in allergic asthma.
abstract: In a murine model of allergic asthma, we found that Tyk-2((-/-)) asthmatic mice have induced peribronchial collagen deposition, mucosal type mast cells in the lung, IRF4 and hyperproliferative lung Th2 CD4(+) effector T cells over-expressing IL-3, IL-4, IL-5, IL-10 and IL-13. We also observed increased Th9 cells expressing IL-9 and IL-10 as well as T helper cells expressing IL-6, IL-10 and IL-21 with a defect in IL-17A and IL-17F production. This T helper phenotype was accompanied by increased SOCS3 in the lung of Tyk-2 deficient asthmatic mice. Finally, in vivo treatment with rIL-17A inhibited local CD4(+)CD25(+)Foxp3(+) T regulatory cells as well as Th2 cytokines without affecting IL-9 in the lung. These results suggest a role of Tyk-2 in different subsets of T helper cells mediated by SOCS3 regulation that is relevant for the treatment of asthma, cancer and autoimmune diseases.
authors.affiliation: 1] Laboratory of Cellular and Molecular Immunology of the Lung, Institute of Molecular Pneumology, University of Erlangen-Nürnberg, 91054 Erlangen, Germany [2].
authors.forename: Caroline
authors.initials: C
authors.lastname: Übel
authors.affiliation: 1] Laboratory of Cellular and Molecular Immunology of the Lung, Institute of Molecular Pneumology, University of Erlangen-Nürnberg, 91054 Erlangen, Germany [2].
authors.forename: Anna
authors.initials: A
authors.lastname: Graser
authors.affiliation: Laboratory of Cellular and Molecular Immunology of the Lung, Institute of Molecular Pneumology, University of Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Koch
authors.affiliation: Institute of Pathology, University of Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors.forename: Ralf J
authors.initials: RJ
authors.lastname: Rieker
authors.affiliation: Institute of Pathology, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland.
authors.forename: Hans A
authors.initials: HA
authors.lastname: Lehr
authors.affiliation: Institute for Animal Breeding and Genetics, University of Veterinary Medicine Vienna, 1210 Vienna, Austria.
authors.forename: Mathias
authors.initials: M
authors.lastname: Müller
authors.affiliation: Laboratory of Cellular and Molecular Immunology of the Lung, Institute of Molecular Pneumology, University of Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors.forename: Susetta
authors.initials: S
authors.lastname: Finotto
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D008168:Lung / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D010641:Phenotype; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D053634:TYK2 Kinase / Q000235:genetics / Q000378:metabolism*; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D020381:Interleukin-17; D011994:Recombinant Proteins; C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D010047:Ovalbumin; D053634:TYK2 Kinase; C499356:Tyk2 protein, mouse
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