Another role of Dicer

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Another roll of the Dice(r)
The ribonuclease III enzyme Dicer is required for CD4+CD25+ regulatory T (TReg) cell development and for the efficient induction of transcription factor forkhead box P3 (FOXP3) expression by transforming growth factor (TGF ).
New findings in The Journal of Experimental Medicine show that naturally occurring CD4+CD25+ regulatory T (TReg) cells and conventional CD4+ (CD25-) T cells have distinct microRNA (miRNA) profiles, and that the ribonuclease III enzyme Dicer, which is required for embryonic development, is involved in the development of TReg cells.
Mature miRNAs are short (21–22 nucleotides), single-stranded RNAs that are generated from longer precursors by Dicer. miRNAs regulate gene expression at the post-transcriptional level by targeting matching pieces of messenger RNA for degradation, thereby decreasing the production of the corresponding protein, and they have been proposed to have a role in haematopoiesis. In their study of TReg-cell biology, Cobb et al. analysed miRNA expression in both TReg cells and conventional CD4+ T cells in mice. These two cell populations had distinctly different expression profiles, with 68 miRNAs being differentially expressed between TReg cells and CD4+ T cells. Interestingly, on activation, CD4+ T cells transiently adopted a profile of miRNA expression that was similar to that of TReg cells. Forced expression of the transcription factor forkhead box P3 (FOXP3), a major marker and regulator of the development and function of mouse TReg cells, in CD4+ T cells showed that 9 of the 10 miRNAs that were upregulated in FOXP3-expressing cells were among the top 20 miRNAs preferentially expressed in TReg cells. Therefore, either directly or indirectly, FOXP3 was contributing to the TReg-cell miRNA expression profile.
Deletion of Dicer from the T-cell lineage resulted in the absence of miRNA expression, reduced numbers of TReg cells and the development of immune pathology in the colon, lung and liver of a proportion of the mice examined. But is Dicer involved in TReg-cell differentiation, or in TReg-cell maintenance or homeostasis? Further investigation focused on the first wave of TReg-cell development in the thymus and revealed that thymic differentiation of Dicer-deficient (and therefore also mature miRNA-deficient) TReg cells was impaired. The induction of FOXP3 in peripheral naive CD4+ T cells by transforming growth factor- (TGF ) was also compromised in the absence of Dicer.
In a cell-autonomous manner, therefore, Dicer is required to maintain normal numbers of TReg cells in peripheral lymphoid organs, for TReg-cell development in the thymus and for the efficient induction of FOXP3 expression by TGF in CD4+ T cells. These findings indicate a novel role for Dicer in immune regulation.

References
1. Cobb, B. S. et al. A role for Dicer in immune regulation. J. Exp. Med. 2006

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