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¹ Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065
² Helen L. and Martin S. Kimmel Center for Biology and Medicine in the Skirball Institute for Biomolecular Medicine and ³ Department of Pathology, New York University School of Medicine, New York, NY 10016
⁴ Department of Immunology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065
⁵ Howard Hughes Medical Institute, Chevy Chase, MD 20815

CORRESPONDENCE Guillaume Darrasse-Jèze: gdarrasse{at}rockefeller.edu

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 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.

© 2009 Darrasse-Jèze et al.
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