Abstract |
Th cell programming and function is tightly regulated by complex biological networks to prevent excessive inflammatory responses and autoimmune disease. The importance of microRNAs ( miRNAs) in this process is highlighted by the preferential Th1 polarization of Dicer-deficient T cells that lack miRNAs. Using genetic knockouts, we demonstrate that loss of endogenous miR-29, derived from the miR-29ab1 genomic cluster, results in unrestrained T-bet expression and IFN-γ production. miR-29b regulates T-bet and IFN-γ via a direct interaction with the 3' untranslated regions, and IFN-γ itself enhances miR-29b expression, establishing a novel regulatory feedback loop. miR-29b is increased in memory CD4(+) T cells from multiple sclerosis (MS) patients, which may reflect chronic Th1 inflammation. However, miR-29b levels decrease significantly upon T cell activation in MS patients, suggesting that this feedback loop is dysregulated in MS patients and may contribute to chronic inflammation. miR-29 thus serves as a novel regulator of Th1 differentiation, adding to the understanding of T cell-intrinsic regulatory mechanisms that maintain a balance between protective immunity and autoimmunity.
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Authors | Kristen M Smith, Mireia Guerau-de-Arellano, Stefan Costinean, Jessica L Williams, Arianna Bottoni, Gina Mavrikis Cox, Abhay R Satoskar, Carlo M Croce, Michael K Racke, Amy E Lovett-Racke, Caroline C Whitacre |
Journal | Journal of immunology (Baltimore, Md. : 1950)
(J Immunol)
Vol. 189
Issue 4
Pg. 1567-76
(Aug 15 2012)
ISSN: 1550-6606 [Electronic] United States |
PMID | 22772450
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- MIRN29 microRNA, mouse
- MicroRNAs
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Topics |
- Animals
- Blotting, Northern
- Cell Differentiation
(genetics, immunology)
- Chromatin Immunoprecipitation
- Encephalomyelitis, Autoimmune, Experimental
(genetics, immunology)
- Feedback, Physiological
- Flow Cytometry
- Humans
- Lymphocyte Activation
(genetics, immunology)
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- MicroRNAs
(genetics, immunology, metabolism)
- Multiple Sclerosis
(genetics, immunology)
- Th1 Cells
(immunology)
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