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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...

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Detalles Bibliográficos
Autores principales: Liston, Adrian, Lu, Li-Fan, O'Carroll, Donal, Tarakhovsky, Alexander, Rudensky, Alexander Y.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2526195/
https://www.ncbi.nlm.nih.gov/pubmed/18725526
http://dx.doi.org/10.1084/jem.20081062
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author Liston, Adrian
Lu, Li-Fan
O'Carroll, Donal
Tarakhovsky, Alexander
Rudensky, Alexander Y.
author_facet Liston, Adrian
Lu, Li-Fan
O'Carroll, Donal
Tarakhovsky, Alexander
Rudensky, Alexander Y.
author_sort Liston, Adrian
collection PubMed
description 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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spelling pubmed-25261952009-03-01 Dicer-dependent microRNA pathway safeguards regulatory T cell function Liston, Adrian Lu, Li-Fan O'Carroll, Donal Tarakhovsky, Alexander Rudensky, Alexander Y. J Exp Med Articles 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. The Rockefeller University Press 2008-09-01 /pmc/articles/PMC2526195/ /pubmed/18725526 http://dx.doi.org/10.1084/jem.20081062 Text en © 2008 Liston et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Articles
Liston, Adrian
Lu, Li-Fan
O'Carroll, Donal
Tarakhovsky, Alexander
Rudensky, Alexander Y.
Dicer-dependent microRNA pathway safeguards regulatory T cell function
title Dicer-dependent microRNA pathway safeguards regulatory T cell function
title_full Dicer-dependent microRNA pathway safeguards regulatory T cell function
title_fullStr Dicer-dependent microRNA pathway safeguards regulatory T cell function
title_full_unstemmed Dicer-dependent microRNA pathway safeguards regulatory T cell function
title_short Dicer-dependent microRNA pathway safeguards regulatory T cell function
title_sort dicer-dependent microrna pathway safeguards regulatory t cell function
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2526195/
https://www.ncbi.nlm.nih.gov/pubmed/18725526
http://dx.doi.org/10.1084/jem.20081062
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