The Journal of Experimental Medicine
ELISpot, FluoroSpot and ELISA kits from Mabtech
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online
doi:10.1084/jem.20081062
The Journal of Experimental Medicine, Vol. 205, No. 9, 1993-2004
The Rockefeller University Press, 0022-1007 $30.00
© Liston et al.
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 7789K)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Liston, A.
Right arrow Articles by Rudensky, A. Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Liston, A.
Right arrow Articles by Rudensky, A. Y.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

ARTICLE

 Dicer-dependent microRNA pathway safeguards regulatory T cell function

Adrian Liston1,2, Li-Fan Lu1, Donal O'Carroll3, Alexander Tarakhovsky3, and Alexander Y. Rudensky1

1 Department of Immunology and Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195
2 John Curtin School of Medical Research, Australian National University, Canberra, ACT 0200, Australia
3 The Laboratory for Lymphocyte Signaling, The Rockefeller University, New York, NY 10065

CORRESPONDENCE Alexander Y. Rudensky: aruden{at}u.washington.edu

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.

Abbreviations used: CTLA4, cytotoxic T lymphocyte antigen 4; Ebi3, EBV-induced gene 3; GITR, glucocorticoid-induced TNFR; ICOS, inducible T cell co-stimulator; miRNA, microRNA; qPCR, quantitative PCR; TE, effector T; TN, naive T; YFP, yellow fluorescent protein.

A. Liston and L.-F. Lu contributed equally to this paper.

D. O'Carroll's present address is European Molecular Biology Laboratory, Mouse Biology Unit, 00015 Monterotondo Scalo Rome, Italy.

© 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/).


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS