Mast cells are essential intermediaries in regulatory T-cell tolerance
(2006) Nature : international weekly journal of science — Vol. 442, n° 7106, p. 997-1002 (2006)
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- Authors
Van Snick, Jacques 
- 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.
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Citations
LI, L.-F., Lind, E. F., Gondek, D. C., Bennett, K. A., Gleeson, M. W., Pino-Lagos, K., Scott, Z. A., Coyle, A. J., Reed, J. L., Van Snick, J., Strom, T. B., Zheng, X. X., & Noelle, R. J. (2006). Mast cells are essential intermediaries in regulatory T-cell tolerance. Nature : international weekly journal of science, 442(7106), 997-1002. https://doi.org/10.1038/nature05010 (Original work published 2006)