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Sci Rep. 2014 Aug 11;4:5865. doi: 10.1038/srep05865.

Role of Tyk-2 in Th9 and Th17 cells in allergic asthma.

Author information

1
1] Laboratory of Cellular and Molecular Immunology of the Lung, Institute of Molecular Pneumology, University of Erlangen-Nürnberg, 91054 Erlangen, Germany [2].
2
Laboratory of Cellular and Molecular Immunology of the Lung, Institute of Molecular Pneumology, University of Erlangen-Nürnberg, 91054 Erlangen, Germany.
3
Institute of Pathology, University of Erlangen-Nürnberg, 91054 Erlangen, Germany.
4
Institute of Pathology, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland.
5
Institute for Animal Breeding and Genetics, University of Veterinary Medicine Vienna, 1210 Vienna, Austria.

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.

PMID:
25109392
PMCID:
PMC4127519
DOI:
10.1038/srep05865
[Indexed for MEDLINE]
Free PMC Article

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