Mast cells are essential intermediaries in regulatory T-cell tolerance

Li Fan Lu, Evan 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

Research output: Contribution to journalArticle

558 Citations (Scopus)

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

Fingerprint

Regulatory T-Lymphocytes
Mast Cells
Interleukin-9
Allografts
Peripheral Tolerance
Transplantation Tolerance
Stem Cell Factor
Immunosuppressive Agents
Genes

ASJC Scopus subject areas

  • General

Cite this

Lu, L. F., Lind, E., Gondek, D. C., Bennett, K. A., Gleeson, M. W., Pino-Lagos, K., ... 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

Mast cells are essential intermediaries in regulatory T-cell tolerance. / Lu, Li Fan; Lind, Evan; 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.

In: Nature, Vol. 442, No. 7106, 31.08.2006, p. 997-1002.

Research output: Contribution to journalArticle

Lu, LF, Lind, E, Gondek, DC, Bennett, KA, Gleeson, MW, Pino-Lagos, K, Scott, ZA, Coyle, AJ, Reed, JL, Van Snick, J, Strom, TB, Zheng, XX & Noelle, RJ 2006, 'Mast cells are essential intermediaries in regulatory T-cell tolerance', Nature, vol. 442, no. 7106, pp. 997-1002. https://doi.org/10.1038/nature05010
Lu LF, Lind E, Gondek DC, Bennett KA, Gleeson MW, Pino-Lagos K et al. Mast cells are essential intermediaries in regulatory T-cell tolerance. Nature. 2006 Aug 31;442(7106):997-1002. https://doi.org/10.1038/nature05010
Lu, Li Fan ; Lind, Evan ; 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. / Mast cells are essential intermediaries in regulatory T-cell tolerance. In: Nature. 2006 ; Vol. 442, No. 7106. pp. 997-1002.
@article{24fc49c699224526beef81afd6da3681,
title = "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 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.",
author = "Lu, {Li Fan} and Evan Lind and Gondek, {David C.} and Bennett, {Kathy A.} and Gleeson, {Michael W.} and Karina Pino-Lagos and Scott, {Zachary A.} and Coyle, {Anthony J.} and Reed, {Jennifer L.} and {Van Snick}, Jacques and Strom, {Terry B.} and Zheng, {Xin Xiao} and Noelle, {Randolph J.}",
year = "2006",
month = "8",
day = "31",
doi = "10.1038/nature05010",
language = "English (US)",
volume = "442",
pages = "997--1002",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7106",

}

TY - JOUR

T1 - Mast cells are essential intermediaries in regulatory T-cell tolerance

AU - Lu, Li Fan

AU - Lind, Evan

AU - Gondek, David C.

AU - Bennett, Kathy A.

AU - Gleeson, Michael W.

AU - Pino-Lagos, Karina

AU - Scott, Zachary A.

AU - Coyle, Anthony J.

AU - Reed, Jennifer L.

AU - Van Snick, Jacques

AU - Strom, Terry B.

AU - Zheng, Xin Xiao

AU - Noelle, Randolph J.

PY - 2006/8/31

Y1 - 2006/8/31

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=33748320914&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33748320914&partnerID=8YFLogxK

U2 - 10.1038/nature05010

DO - 10.1038/nature05010

M3 - Article

C2 - 16921386

AN - SCOPUS:33748320914

VL - 442

SP - 997

EP - 1002

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7106

ER -