Dicer-dependent microRNA pathway safeguards regulatory T cell function
Date
2008
Authors
Liston, Adrian
Lu, Li-Fan
O'Carroll, D C
Tarakhovsky, Alexander
Rudensky, Alexander
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Rockefeller University Press
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.
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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 RN
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Source
Journal of Experimental Medicine
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Journal article
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2037-12-31
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