MicroRNAs maintain identity (original) (raw)

Regulatory T cells

Nature Reviews Immunology volume 8, page 752 (2008)Cite this article

TReg cells are known to be essential for immune homeostasis and act by suppressing the activation of autoreactive T cells. Accordingly, the ablation of TReg cells or mutation of the gene that encodes the TReg-cell-defining transcription factor forkhead box P3 (FOXP3) results in a devastating autoimmune lymphoproliferative disease in mice. The new data further support this important function of TReg cells and reveal that microRNAs are required to maintain TReg-cell activity, which befits their suggested role in 'buffering' gene expression in conditions of environmental stress.

MicroRNAs, which regulate gene expression at the post-transcriptional level, are generated from longer RNA transcripts through sequential processing by the enzymes Drosha and Dicer; deletion of these enzymes can therefore be used to study the effects of microRNA deficiency. In all three studies, mice with a TReg-cell-specific deletion of Dicer developed a spontaneous, aggressive autoimmune disease that was indistinguishable from that observed in mice that lack Foxp3 or TReg cells. Chong et al. also found that conditional deletion of Drosha in TReg cells had the same devastating effect, which confirms that Drosha and Dicer function in the same pathway. The finding that mice in which Dicer (or Drosha) was deleted in all T cells suffered a less severe, delayed lymphoproliferative disease suggested that unknown defects in the activation or function of conventional T cells caused by the absence of microRNAs could mask the devastating consequences of Dicer deficiency in TReg cells.

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ORIGINAL RESEARCH PAPERS

  1. Zhou, X. et al. Selective miRNA disruption in T reg cells leads to uncontrolled autoimmunity. J. Exp. Med. 205, 1983–1991 (2008)
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  3. Chong, M. M. W., Rasmussen, J. P., Rudensky, A. Y. & Littman, D. R. The RNAseIII enzyme Drosha is critical in T cells for preventing lethal inflammatory disease. J. Exp. Med. 205, 2005–2017 (2008)
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Bird, L. MicroRNAs maintain identity.Nat Rev Immunol 8, 752 (2008). https://doi.org/10.1038/nri2426

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