Liston, AdrianLu, Li-FanO'Carroll, D CTarakhovsky, AlexanderRudensky, Alexander2015-12-080022-1007http://hdl.handle.net/1885/32393Regulatory T (T reg) cells are indispensable for preventing autoimmunity. Incumbent to this role is the ability of T reg cells to exert their suppressor function under inflammatory conditions. We found that T reg cell-mediated tolerance is critically dependent on the Dicer-controlled microRNA (miRNA) pathway. Depletion of miRNA within the T reg cell lineage resulted in fatal autoimmunity indistinguishable from that in T reg cell-deficient mice. In disease-free mice lacking Dicer in all T cells or harboring both Dicer-deficient and -sufficient T reg cells, Dicer-deficient T reg cells were suppressive, albeit to a lesser degree, whereas their homeostatic potential was diminished as compared with their Dicer-sufficient counterparts. However, in diseased mice, Dicer-deficient T reg cells completely lost suppressor capacity. Thus, miRNA preserve the T reg cell functional program under inflammatory conditions.Keywords: dicer; microRNA; animal experiment; animal tissue; article; autoimmunity; cell function; homeostasis; inflammation; mouse; nonhuman; priority journal; regulatory T lymphocyte; Animals; Apoptosis; Autoimmunity; Cell Lineage; Cell Proliferation; DEAD-box RNDicer-dependent microRNA pathway safeguards regulatory T cell function200810.1084/jem.200810622015-12-08