Mast cells are essential intermediaries in regulatory T-cell tolerance
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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TH2 cells and Treg cells can produce IL-9.
“TH2 cells and Treg cells can produce IL-9 (ref. 28)”
From The transcription factor PU.1 is required for the development of IL-9-producing T cells and allergic inflammation (2010) · cites this paper as [28]
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- Authors
- 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.
- Affiliations
- Dartmouth College (US)
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Noelle, Randolph J.
- ORCID
- Venue
- Nature
- Published
- 2006-08
- Volume
- 442
- Issue
- 7106
- Pages
- 997-1002
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2000648336
- Cited by
- 751
- References
- 0
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 14 · 2023: 21 · 2022: 21 · 2021: 22 · 2020: 26 · 2019: 16 · 2018: 28 · 2017: 31 · 2016: 34 · 2015: 39 · 2014: 43 · 2013: 43 · 2012: 58
- FWCI
- 27.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Digital Access to Libraries (Université catholique de Louvain (UCL), l'Université de Namur (UNamur) and the Université Saint-Louis (USL-B)) (submittedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Keywords
- mast cells, regulatory T cells, peripheral tolerance, allograft tolerance, IL-9, graft rejection, Foxp3, CD4+CD25+ T cells, mast cell recruitment, immunosuppression, mast cell-deficient mice, tissue transplantation
- MeSH terms
- Animals, Cell Count, Gene Expression Regulation, Graft Rejection, Immune Tolerance, Mast Cells, Mice, Inbred Strains, Skin, Time Factors, Transplantation, Homologous, Skin Transplantation, Interleukin-9, T-Lymphocytes, Regulatory, Mice
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