Mast cells are essential intermediaries in regulatory T-cell tolerance

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.

Más información

Título según WOS: ID WOS:000240142000039 Not found in local WOS DB
Título de la Revista: NATURE
Volumen: 442
Número: 7106
Editorial: Nature Research
Fecha de publicación: 2006
Página de inicio: 997
Página final: 1002
DOI:

10.1038/nature05010

Notas: ISI