Dicer-dependent microRNA pathway safeguards regulatory T cell function.
Regulatory 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.
Liston
Adrian
A
Department of Immunology and Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.
Lu
Li-Fan
LF
O'Carroll
Donal
D
Tarakhovsky
Alexander
A
Rudensky
Alexander Y
AY
D000818:Animals; D017209:Apoptosis; D015551:Autoimmunity; D019070:Cell Lineage; D049109:Cell Proliferation; D053487:DEAD-box RNA Helicases / Q000235:genetics* / Q000502:physiology*; D004722:Endoribonucleases / Q000235:genetics* / Q000502:physiology*; D007107:Immune System; D007108:Immune Tolerance; D007249:Inflammation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000378:metabolism; D043244:Ribonuclease III; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*
D035683:MicroRNAs; D004722:Endoribonucleases; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases