| First Author | Darrasse-Jèze G | Year | 2009 |
| Journal | J Exp Med | Volume | 206 |
| Issue | 9 | Pages | 1853-62 |
| PubMed ID | 19667061 | Mgi Jnum | J:152171 |
| Mgi Id | MGI:4356379 | Doi | 10.1084/jem.20090746 |
| Citation | Darrasse-Jeze G, et al. (2009) Feedback control of regulatory T cell homeostasis by dendritic cells in vivo. J Exp Med 206(9):1853-62 |
| abstractText | 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. |
