| First Author | Lu LF | Year | 2006 |
| Journal | Nature | Volume | 442 |
| Issue | 7106 | Pages | 997-1002 |
| PubMed ID | 16921386 | Mgi Jnum | J:112226 |
| Mgi Id | MGI:3655890 | Doi | 10.1038/nature05010 |
| Citation | Lu LF, et al. (2006) Mast cells are essential intermediaries in regulatory T-cell tolerance. Nature 442(7106):997-1002 |
| abstractText | 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. |
