Mast cells are essential intermediaries in regulatory T-cell tolerance
| Autor: | Kathy A. Bennett, Randolph J. Noelle, Michael W Gleeson, Evan F. Lind, Xin Xiao Zheng, Li-Fan Lu, Anthony J. Coyle, Karina Pino-Lagos, Zachary A. Scott, Jacques Van Snick, David C. Gondek, Jennifer L. Reed, Terry B. Strom |
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| Rok vydání: | 2006 |
| Předmět: | |
| Zdroj: | Nature. 442:997-1002 |
| ISSN: | 1476-4687 0028-0836 |
| DOI: | 10.1038/nature05010 |
| Popis: | Contrary to the proinflammatory role of mast cells in allergic disorders, the results obtained in this study establish that mast cells are essential in CD4(+)CD25(+)Foxp3(+) regulatory T (T-Reg)-cell-dependent peripheral tolerance. Here we confirm that tolerant allografts, which are sustained owing to the immunosuppressive effects of T-Reg cells, acquire a unique genetic signature dominated by the expression of mast-cell-gene products. We also show that mast cells are crucial for allograft tolerance, through the inability to induce tolerance in mast-cell-deficient mice. High levels of interleukin (IL)-9 - a mast cell growth and activation factor - are produced by activated T-Reg cells, and IL-9 production seems important in mast cell recruitment to, and activation in, tolerant tissue. Our data indicate that IL-9 represents the functional link through which activated T-Reg cells recruit and activate mast cells to mediate regional immune suppression, because neutralization of IL-9 greatly accelerates allograft rejection in tolerant mice. Finally, immunohistochemical analysis clearly demonstrates the existence of this novel T-Reg - IL-9-mast cell relationship within tolerant allografts. |
| Databáze: | OpenAIRE |
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