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

Details

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State: Public
Version: Final published version
Serval ID
serval:BIB_A417AA7476AB
Type
Article: article from journal or magazin.
Collection
Publications
Title
Role of Tyk-2 in Th9 and Th17 cells in allergic asthma.
Journal
Scientific reports
Author(s)
Übel C., Graser A., Koch S., Rieker R.J., Lehr H.A., Müller M., Finotto S.
ISSN
2045-2322 (Electronic)
ISSN-L
2045-2322
Publication state
Published
Issued date
11/08/2014
Peer-reviewed
Oui
Volume
4
Pages
5865
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
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.

Keywords
Animals, Asthma/immunology, Asthma/metabolism, Asthma/pathology, CD4-Positive T-Lymphocytes/cytology, CD4-Positive T-Lymphocytes/immunology, Cell Differentiation, Cell Proliferation, Cytokines/metabolism, Disease Models, Animal, Interleukin-17/genetics, Interleukin-17/metabolism, Interleukin-17/pharmacology, Lung/metabolism, Mice, Mice, Inbred BALB C, Mice, Knockout, Ovalbumin/immunology, Phenotype, Recombinant Proteins/biosynthesis, Recombinant Proteins/genetics, Recombinant Proteins/pharmacology, Suppressor of Cytokine Signaling 3 Protein, Suppressor of Cytokine Signaling Proteins/metabolism, T-Lymphocytes, Helper-Inducer/drug effects, T-Lymphocytes, Helper-Inducer/immunology, T-Lymphocytes, Helper-Inducer/metabolism, TYK2 Kinase/genetics, TYK2 Kinase/metabolism, Th17 Cells/cytology, Th17 Cells/immunology, Th17 Cells/metabolism, Th2 Cells/cytology, Th2 Cells/immunology, Th2 Cells/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
19/09/2014 18:00
Last modification date
20/08/2019 16:09
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