title: The miR-17 ∼ 92a cluster of microRNAs is required for the fitness of Foxp3+ regulatory T cells.
abstract: By genetic inactivation of key microRNA biogenesis enzymes, we and others have previously demonstrated the critical requirement of the microRNA pathway for the differentiation and function of Foxp3(+) regulatory T cells. In this study, we identified members of the miR-17 ∼ 92a cluster of microRNAs to be enriched in regulatory T cells. To investigate the function of this microRNA cluster, we deleted the gene specifically in Foxp3(+) cells in mice. We found that miR-17 ∼ 92a is required for the fitness of regulatory T cells, and deficiency impacted at the level of apoptosis and proliferation of these cells. This led to a loss of Foxp3(+) cells over time, particularly in competitive settings, and culminated in a range of immunologic perturbations. Thus, miR-17 ∼ 92a-target interactions are part of the essential microRNA networks that safeguard the regulatory T cell lineage.
authors: St Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia.
authors: Jarrod P J
authors: JP
authors: Skinner
authors: St Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia.
authors: Ashleigh A
authors: AA
authors: Keown
authors: St Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia ; Department of Medicine (St Vincent's), University of Melbourne, Fitzroy, Victoria, Australia.
authors: Mark M W
authors: MM
authors: Chong
mesh_terms: D000483:Alleles; D000818:Animals; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000166:cytology; D019070:Cell Lineage; D049109:Cell Proliferation; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D053263:Gene Regulatory Networks; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics*; D005810:Multigene Family; D050378:T-Lymphocytes, Regulatory / Q000166:cytology*
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D035683:MicroRNAs; C543614:Mirn17 microRNA, mouse; C541873:Mirn92 microRNA, mouse