TY - JOUR
T1 - Dicer-dependent microRNA pathway safeguards regulatory T cell function
AU - Liston, Adrian
AU - Lu, Li Fan
AU - O'Carroll, Donal
AU - Tarakhovsky, Alexander
AU - Rudensky, Alexander Y.
PY - 2008/9/1
Y1 - 2008/9/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=51049110261&partnerID=8YFLogxK
U2 - 10.1084/jem.20081062
DO - 10.1084/jem.20081062
M3 - Article
SN - 0022-1007
VL - 205
SP - 1993
EP - 2004
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 9
ER -