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- Title
Mast cells are essential intermediaries in regulatory T-cell tolerance.
- Authors
Lu, Li-Fan; Lind, Evan F; Gondek, David C; Bennett, Kathy A; Gleeson, Michael W; Pino-Lagos, Karina; Scott, Zachary A; Coyle, Anthony J; Reed, Jennifer L; Van Snick, Jacques; Strom, Terry B; Zheng, Xin Xiao; Noelle, Randolph J
- Abstract
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.
- Publication
Nature, 2006, Vol 442, Issue 7106, p997
- ISSN
1476-4687
- Publication type
Journal Article
- DOI
10.1038/nature05010