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Dicer-dependent microRNA pathway safeguards regulatory T cell function.

TitleDicer-dependent microRNA pathway safeguards regulatory T cell function.
Publication TypeJournal Article
Year of Publication2008
AuthorsListon A, Lu L-F, O'Carroll D, Tarakhovsky A, Rudensky AY
JournalJ Exp Med
Volume205
Issue9
Pagination1993-2004
Date Published2008 Sep 1
ISSN1540-9538
KeywordsAnimals, Apoptosis, Autoimmunity, Cell Lineage, Cell Proliferation, DEAD-box RNA Helicases, Endoribonucleases, Immune System, Immune Tolerance, Inflammation, Mice, Mice, Inbred C57BL, Mice, Transgenic, MicroRNAs, Ribonuclease III, T-Lymphocytes, Regulatory
Abstract

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.

DOI10.1084/jem.20081062
Alternate JournalJ. Exp. Med.
PubMed ID18725526
PubMed Central IDPMC2526195
Grant List / / Howard Hughes Medical Institute / United States
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