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Journal Article
Mast cells are essential intermediaries in regulatory T-cell tolerance
2006
Overview
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.
Mast Cells and Graft Rejection
Mast cells are important immune system components, best known as responders in allergic reactions such as anaphylaxis and asthma. Recent work suggests that they also act as immunoregulatory cells in both innate and adaptive immunity and surprisingly, gene expression profiles point to an association with tolerance to tissue transplants. Studies in mice now confirm that mast cells
are
major cellular players in immune suppression, needed for peripheral suppression dependent on regulatory T cells. This also implies a role for interleukin 9 (IL-9) as a link between activated T cells and mast cell recruitment and makes IL-9, mast cells and their gene products of interest as targets for drugs to prevent graft rejection.
Publisher
Nature Publishing Group UK,Nature Publishing,Nature Publishing Group
Subject
/ Animals
/ Biological and medical sciences
/ Fundamental and applied biological sciences. Psychology
/ Gene Expression Regulation - genetics
/ Graft Rejection - immunology
/ Humanities and Social Sciences
/ Immune Tolerance - immunology
/ Mice
/ Rodents
/ Science
/ Skin Transplantation - immunology
