Itk is required for Th9 differentiation via TCR-mediated induction of IL-2 and IRF4
| Autor: | Françoise Meylan, Julio Gomez-Rodriguez, Pamela L. Schwartzberg, Martha Kirby, Erika T. Hayes, Robin Handon, Richard M. Siegel, Stacie M. Anderson |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
CD4-Positive T-Lymphocytes
Lung Diseases Male 0301 basic medicine Interleukin 2 medicine.medical_treatment T cell Cellular differentiation Science Immunology Regulator General Physics and Astronomy Article General Biochemistry Genetics and Molecular Biology Mice 03 medical and health sciences Immune system Interferon Papain medicine Animals Immunology and Allergy Mice Knockout Multidisciplinary Chemistry T-cell receptor Cell Differentiation General Chemistry Protein-Tyrosine Kinases 030104 developmental biology Cytokine medicine.anatomical_structure Gene Expression Regulation Interferon Regulatory Factors Cancer research Interleukin-2 Female Protein Kinases medicine.drug |
| Zdroj: | Nature Communications, Vol 7, Iss 1, Pp 1-15 (2016) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | Th9 cells produce interleukin (IL)-9, a cytokine implicated in allergic asthma and autoimmunity. Here we show that Itk, a mediator of T cell receptor signalling required for Th2 immune responses and the development of asthma, is a positive regulator of Th9 differentiation. In a model of allergic lung disease, Itk-deficient mice show reduced pulmonary inflammation and IL-9 production by T cells and innate lymphoid type 2 cells (ILC2), despite normal early induction of ILC2s. In vitro, Itk−/− CD4+ T cells do not produce IL-9 and have reduced levels of IRF4 (Interferon Regulator Factor 4), a critical transcription factor for effector T cell function. Both IL-9 and IRF4 expression are rescued by either IL-2 or constitutively active STAT5, but not NFATc1. STAT5 binds the Irf4 promoter, demonstrating one mechanism by which IL-2 rescues weakly activated T cells. Itk inhibition also reduces IL-9 expression by human T cells, implicating ITK as a key regulator of Th9 induction. The Tec family tyrosine kinase, Itk, is a component of the T-cell receptor essential for optimal Th2 responses in vivo. Here the authors show in human cells and mouse models that Itk is also needed for the production of IL-9, an important contributor to allergic asthma. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|