Feedback control of regulatory T cell homeostasis by dendritic cells in vivo.
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 (...
| Main Authors: | , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2009
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| _version_ | 1797070712785076224 |
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| author | Darrasse-Jèze, G Deroubaix, S Mouquet, H Victora, G Eisenreich, T Yao, K Masilamani, R Dustin, M Rudensky, A Liu, K Nussenzweig, M |
| author_facet | Darrasse-Jèze, G Deroubaix, S Mouquet, H Victora, G Eisenreich, T Yao, K Masilamani, R Dustin, M Rudensky, A Liu, K Nussenzweig, M |
| author_sort | Darrasse-Jèze, G |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T22:42:54Z |
| format | Journal article |
| id | oxford-uuid:5c32a400-524e-45be-a36c-07816a433437 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:42:54Z |
| publishDate | 2009 |
| record_format | dspace |
| spelling | oxford-uuid:5c32a400-524e-45be-a36c-07816a4334372022-03-26T17:26:39ZFeedback control of regulatory T cell homeostasis by dendritic cells in vivo.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:5c32a400-524e-45be-a36c-07816a433437EnglishSymplectic Elements at Oxford2009Darrasse-Jèze, GDeroubaix, SMouquet, HVictora, GEisenreich, TYao, KMasilamani, RDustin, MRudensky, ALiu, KNussenzweig, MCD4(+)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. |
| spellingShingle | Darrasse-Jèze, G Deroubaix, S Mouquet, H Victora, G Eisenreich, T Yao, K Masilamani, R Dustin, M Rudensky, A Liu, K Nussenzweig, M Feedback control of regulatory T cell homeostasis by dendritic cells in vivo. |
| title | Feedback control of regulatory T cell homeostasis by dendritic cells in vivo. |
| title_full | Feedback control of regulatory T cell homeostasis by dendritic cells in vivo. |
| title_fullStr | Feedback control of regulatory T cell homeostasis by dendritic cells in vivo. |
| title_full_unstemmed | Feedback control of regulatory T cell homeostasis by dendritic cells in vivo. |
| title_short | Feedback control of regulatory T cell homeostasis by dendritic cells in vivo. |
| title_sort | feedback control of regulatory t cell homeostasis by dendritic cells in vivo |
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