Signature cytokine-associated transcriptome analysis of effector γδ T cells identifies subset-specific regulators of peripheral activation.

γδ T cells producing either interleukin-17A (γδ cells) or interferon-γ (γδ cells) are generated in the mouse thymus, but the molecular regulators of their peripheral functions are not fully characterized. Here we established an Il17a-GFP:Ifng-YFP double-reporter mouse strain to analyze at unprecedented depth the transcriptomes of pure γδ cell versus γδ cell populations from peripheral lymph nodes. Within a very high fraction of differentially expressed genes, we identify a panel of 20 new signature genes in steady-state γδ cells versus γδ cells, which we further validate in models of experimental autoimmune encephalomyelitis and cerebral malaria, respectively.

MicroRNA-181a regulates IFN-γ expression in effector CD8 T cell differentiation.

CD8 T cells are key players in immunity against intracellular infections and tumors. The main cytokine associated with these protective responses is interferon-γ (IFN-γ), whose production is known to be regulated at the transcriptional level during CD8 T cell differentiation. Here we found that microRNAs constitute a posttranscriptional brake to IFN-γ expression by CD8 T cells, since the genetic interference with the Dicer processing machinery resulted in the overproduction of IFN-γ by both thymic and peripheral CD8 T cells.

Control of T cell effector functions by miRNAs.

The differentiation of effector T cells is a tightly regulated process that relies on the selective expression of lineage-defining master regulators that orchestrate unique transcriptional programs, including the production of distinct sets of effector cytokines. miRNAs are post-transcriptional regulators that are now viewed as critical players in these gene expression networks and help defining cell identity and function. This review summarises the role of individual miRNAs in the regulation of the differentiation of effector T cell subsets, including CD4 T helper cells, cytotoxic CD8 T cells and innate-like NKT cells.