| Abstract: |
CD4<sup>+</sup>CD25<sup>+</sup>Foxp3<sup>+</sup> 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 γ 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. |
| Keywords: |
controlled study; protein expression; nonhuman; treatment planning; flow cytometry; transcription factor foxp3; cell proliferation; forkhead transcription factors; animal cell; mouse; animals; mice; animal tissue; cell division; dendritic cell; animal experiment; animal model; in vivo study; mice, transgenic; cytokine; regulatory t lymphocyte; antigen presentation; cytokines; dendritic cells; antibodies, monoclonal; correlation analysis; gamma interferon; t-lymphocytes, regulatory; major histocompatibility antigen class 2; enteritis; feedback system; interleukin 17; th17 cell; inflammatory bowel diseases; th1 cell; flt3 ligand; autoimmune disease; homeostasis; insulin dependent diabetes mellitus; major histocompatibility complex; diabetes mellitus, type 1; feedback; genes, mhc class ii; mice, inbred nod; regression analysis
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