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Decreased STAT5 phosphorylation and GATA-3 expression in NOX2-deficient T cells: Role in T helper development
| Content Provider | Scilit |
|---|---|
| Author | Shatynski, Kristen E. Chen, Haiyan Kwon, Jaeyul Williams, Mark S. |
| Copyright Year | 2012 |
| Description | Journal: European Journal of Immunology Absence of phagocyte NADPH oxidase (NOX2) activity causes chronic granulomatous disease (CGD), a primary immunodeficiency characterized by recurrent bacterial infections. In contrast to this innate immune deficit, CGD patients and animal models display a predisposition toward autoimmune disease and enhanced response to Helicobacter pylori and influenza virus infection. These data imply an altered, perhaps augmented, adaptive immune response in CGD. As previous data demonstrated functional NOX2 expression in T cells, our goal here was to determine if NOX2-deficient T cells are inherently altered in their responses. Activation of purified naive CD4(+) T cells from NOX2-deficient mice led to augmented IFN-γ and diminished IL-4 production and an increased ratio of expression of the T(H)1-specific transcription factor T-bet versus the T(H)2-specfic transcription factor GATA-3, consistent with a T(H)1 skewing of naïve T cells. Selective inhibition of TCR-induced STAT5 phosphorylation was identified as a potential mechanism for skewed T helper differentiation. Exposure to antioxidants inhibited, while pro-oxidants augmented T(H)2 cytokine secretion and STAT5 phosphorylation, supporting the redox dependence of these signaling changes. These data suggest that TCR-induced ROS generation from NOX2 activation can regulate the adaptive immune response in a T-cell-inherent fashion, and propose a possible role for redox signaling in T helper differentiation. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3691816/pdf |
| Ending Page | 3211 |
| Page Count | 10 |
| Starting Page | 3202 |
| e-ISSN | 15214141 |
| DOI | 10.1002/eji.201242659 |
| Journal | European Journal of Immunology |
| Issue Number | 12 |
| Volume Number | 42 |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 2012-10-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: European Journal of Immunology Chronic Granulomatous Disease Nadph Oxidase Reactive Oxygen Species |
| Content Type | Text |
| Resource Type | Article |