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J Exp Med. 2009 Aug 31;206(9):1853-62. doi: 10.1084/jem.20090746. Epub 2009 Aug 10.

Feedback control of regulatory T cell homeostasis by dendritic cells in vivo.

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1
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA. gdarrasse@rockefeller.edu

Abstract

CD4(+)CD25(+)Foxp3(+) natural regulatory T cells (T reg cells) maintain self-tolerance and suppress autoimmune diseases such as type 1 diabetes and inflammatory bowel disease (IBD). In addition to their effects on T cells, T reg cells are essential for maintaining normal numbers of dendritic cells (DCs): when T reg cells are depleted, there is a compensatory Flt3-dependent increase in DCs. However, little is known about how T reg cell homeostasis is maintained in vivo. We demonstrate the existence of a feedback regulatory loop between DCs and T reg cells. We find that loss of DCs leads to a loss of T reg cells, and that the remaining T reg cells exhibit decreased Foxp3 expression. The DC-dependent loss in T reg cells leads to an increase in the number of T cells producing inflammatory cytokines, such as interferon gamma and interleukin 17. Conversely, increasing the number of DCs leads to increased T reg cell division and accumulation by a mechanism that requires major histocompatibility complex II expression on DCs. The increase in T reg cells induced by DC expansion is sufficient to prevent type 1 autoimmune diabetes and IBD, which suggests that interference with this feedback loop will create new opportunities for immune-based therapies.

PMID:
19667061
PMCID:
PMC2737156
DOI:
10.1084/jem.20090746
[Indexed for MEDLINE]
Free PMC Article
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