Role of Itk in Th17 mediated inflammation model hypersensitivity pneumonitis (IRC8P.491)
| Autor: | Chavez Carter |
|---|---|
| Rok vydání: | 2014 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 192:190.19-190.19 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Hypersensitivity Pneumonitis (HP) is a lung disease caused by repeated inhalation of environmental antigens leading to inflammation, tissue scarring, and loss of lung function. This pathology is believed to be due to the increased IL-17A, a cytokine secreted primarily by Th17 cells that induces recruitment of inflammatory cells such as neutrophils. The thermophile Sacharopolyspora rectivigula (SR) causes HP, using a murine model of SR exposure; we study the molecular mechanism of this disease development. Using novel IL-17A-GFP reporter mice, our data suggests that the high levels of IL-17A induced in response to SR are produced in part by CD4+ T cells and not neutrophils. The Tec family tyrosine kinase Itk regulates T cell activation and cytokine production in conventional Th17 cells but Itk-/- mice still develop HP. Histology shows an increase in inflammatory cells in lung airways as well as decline of lung tissue architecture. Itk-/- lungs also have high levels of IL-17A mRNA expression, and an increase in the number of CD4+ IL-17A producing cells. However, Itk-/- mice lack IL-17A producing γδ T cells in the early stage of HP, which recovers in the later stage. This directly coincides with the emergence of IL-17A producing CD4+γδ T cells in the lungs of Itk-/- mice exposed to SR. We conclude that Itk regulated signals are not critical for the production of IL-17A in response to SR, and Itk may differentially regulate the production of IL-17A in different types of T cells. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|