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

Language
en
Document Type
Article
Issue Date
2015-03-02
Issue Year
2014
Authors
Übel, Caroline
Graser, Anna
Koch, Sonja
Rieker, Ralf J.
Lehr, Hans A.
Müller, Mathias
Finotto, Susetta
Editor
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.

Journal Title
Scientific Reports
Volume
4
Issue
5865
Citation
Scientific Reports 4.5865 (2014). <http://www.nature.com/srep/2014/140811/srep05865/full/srep05865.html>
DOI
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