Mast cells are essential intermediaries in regulatory T-cell tolerance

Li Fan Lu, Evan F. Lind, David C. Gondek, Kathy A. Bennett, Michael W. Gleeson, Karina Pino-Lagos, Zachary A. Scott, Anthony J. Coyle, Jennifer L. Reed, Jacques Van Snick, Terry B. Strom, Xin Xiao Zheng, Randolph J. Noelle

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577 Scopus citations

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 TReg 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 TReg 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 TReg 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 TReg-IL-9- mast cell relationship within tolerant allografts.

Original languageEnglish (US)
Pages (from-to)997-1002
Number of pages6
JournalNature
Volume442
Issue number7106
DOIs
StatePublished - Aug 31 2006
Externally publishedYes

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    Lu, 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, 442(7106), 997-1002. https://doi.org/10.1038/nature05010