Journal
NATURE IMMUNOLOGY
Volume 15, Issue 4, Pages 393-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.2846
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Funding
- Arthritis Foundation
- Deutsche Forschungsgemeinschaft
- National Basic Research Program of China [2013CB967002]
- Keck Foundation
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The microRNA miR-210 is a signature of hypoxia. We found robust increase in the abundance of miR-210 (>100-fold) in activated T cells, especially in the T(H)17 lineage of helper T cells. Hypoxia acted in synergy with stimulation via the T cell antigen receptor (TCR) and coreceptor CD28 to accelerate and increase Mir210 expression. Mir210 was directly regulated by HIF-1 alpha, a key transcriptional regulator of TH17 polarization. Unexpectedly, we identified Hif1a as a target of miR-210, which suggested negative feedback by miR-210 in inhibiting HIF-1 alpha expression. Deletion of Mir210 promoted TH17 differentiation under conditions of limited oxygen. In experimental colitis, miR-210 reduced the abundance of Hif1a transcripts and the proportion of cells that produced inflammatory cytokines and controlled disease severity. Our study identifies miR-210 as an important regulator of T cell differentiation in hypoxia, which can limit immunopathology.
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