User menu

Accès à distance ? S'identifier sur le proxy UCLouvain

Mast cells are essential intermediaries in regulatory T-cell tolerance

Primary tabs

LI, Li-Fan Lind, Evan F. Gondek, David C. Bennett, Kathy A. Gleeson, Michael W. Van Snick, Jacques [UCL] Noelle, Randolph J.

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.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès restreint
Publication date 2006
Language Anglais
Journal information "Nature : international weekly journal of science" - Vol. 442, no. 7106, p. 997-1002 (2006)
Peer reviewed yes
Publisher Nature Publishing Group (London)
issn 0028-0836
e-issn 1476-4687
Publication status Publié
Affiliation UCL - Autre
Links
  1. Sakaguchi Shimon, Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self, 10.1038/ni1178
  2. Quezada S. A., Bennett K., Blazar B. R., Rudensky A. Y., Sakaguchi S., Noelle R. J., Analysis of the Underlying Cellular Mechanisms of Anti-CD154-Induced Graft Tolerance: The Interplay of Clonal Anergy and Immune Regulation, 10.4049/jimmunol.175.2.771
  3. Taylor Patricia A., Noelle Randolph J., Blazar Bruce R., Cd4+Cd25+Immune Regulatory Cells Are Required for Induction of Tolerance to Alloantigen via Costimulatory Blockade, 10.1084/jem.193.11.1311
  4. Galli Stephen J, Nakae Susumu, Tsai Mindy, Mast cells in the development of adaptive immune responses, 10.1038/ni1158
  5. Galli Stephen J., Kalesnikoff Janet, Grimbaldeston Michele A., Piliponsky Adrian M., Williams Cara M.M., Tsai Mindy, MAST CELLS AS “TUNABLE” EFFECTOR AND IMMUNOREGULATORY CELLS: Recent Advances, 10.1146/annurev.immunol.21.120601.141025
  6. Benoist Christophe, Mathis Diane, Mast cells in autoimmune disease, 10.1038/nature01324
  7. Zelenika Diana, Adams Elizabeth, Humm Susan, Lin Chun-Yen, Waldmann Herman, Cobbold Stephen P., The role of CD4+ T-cell subsets in determining transplantation rejection or tolerance, 10.1034/j.1600-065x.2001.1820113.x
  8. Graca Luis, Cobbold Stephen P., Waldmann Herman, Identification of Regulatory T Cells in Tolerated Allografts, 10.1084/jem.20012097
  9. Hara M., Kingsley C. I., Niimi M., Read S., Turvey S. E., Bushell A. R., Morris P. J., Powrie F., Wood K. J., IL-10 Is Required for Regulatory T Cells to Mediate Tolerance to Alloantigens In Vivo, 10.4049/jimmunol.166.6.3789
  10. Corti B., Altimari A., Gabusi E., Pinna A.D., Lauro A., Morselli-Labate A.M., Gruppioni E., Pirini M.G., Fiorentino M., Ridolfi L., Grigioni W.F., D’Errico-Grigioni A., Potential of Real-Time PCR Assessment of Granzyme B and Perforin Up-Regulation for Rejection Monitoring in Intestinal Transplant Recipients, 10.1016/j.transproceed.2005.11.035
  11. Wang H. W., J. Clin. Invest., 102, 1617 (1998)
  12. Berrozpe G., Blood, 94, 2658 (1999)
  13. Yamazaki M., Blood, 83, 3509 (1994)
  14. Grimbaldeston Michele A., Chen Ching-Cheng, Piliponsky Adrian M., Tsai Mindy, Tam See-Ying, Galli Stephen J., Mast Cell-Deficient W-sash c-kit Mutant KitW-sh/W-sh Mice as a Model for Investigating Mast Cell Biology in Vivo, 10.1016/s0002-9440(10)62055-x
  15. Van Snick J., Cloning and characterization of a cDNA for a new mouse T cell growth factor (P40), 10.1084/jem.169.1.363
  16. Jarnicki A. G., Curr. Opin. Pharmacol., 3, 449 (2003)
  17. Zhou Yuhong, McLane Michael, Levitt Roy C, 10.1186/rr42
  18. Townsend Michael J, Fallon Padraic G, Matthews David J, Smith Philip, Jolin Helen E, McKenzie Andrew N.J, IL-9-Deficient Mice Establish Fundamental Roles for IL-9 in Pulmonary Mastocytosis and Goblet Cell Hyperplasia but Not T Cell Development, 10.1016/s1074-7613(00)00056-x
  19. Shimizu Jun, Yamazaki Sayuri, Takahashi Takeshi, Ishida Yasumasa, Sakaguchi Shimon, Stimulation of CD25+CD4+ regulatory T cells through GITR breaks immunological self-tolerance, 10.1038/ni759
  20. Tone M., Tone Y., Adams E., Yates S. F., Frewin M. R., Cobbold S. P., Waldmann H., Mouse glucocorticoid-induced tumor necrosis factor receptor ligand is costimulatory for T cells, 10.1073/pnas.2334901100
  21. Chen WanJun, Jin Wenwen, Hardegen Neil, Lei Ke-jian, Li Li, Marinos Nancy, McGrady George, Wahl Sharon M., Conversion of Peripheral CD4+CD25−Naive T Cells to CD4+CD25+Regulatory T Cells by TGF-β Induction of Transcription FactorFoxp3, 10.1084/jem.20030152
  22. Jarvinen L. Z., Transplantation, 76, 1375 (2003)
  23. Theoharides Theoharis C., Conti Pio, Mast cells: the JEKYLL and HYDE of tumor growth, 10.1016/j.it.2004.02.013
  24. Mesplès Bettina, Fontaine Romain H., Lelièvre Vincent, Launay Jean-Marie, Gressens Pierre, Neuronal TGF-β1 mediates IL-9/mast cell interaction and exacerbates excitotoxicity in newborn mice, 10.1016/j.nbd.2004.09.018
  25. Lee Geon Kook, Park Hyeon Jin, Macleod Megan, Chandler Phillip, Munn David H., Mellor Andrew L., Tryptophan deprivation sensitizes activated T cells to apoptosis prior to cell division, 10.1046/j.1365-2567.2002.01526.x
  26. Wedemeyer Jochen, Galli Stephen J, Decreased susceptibility of mast cell-deficient KitW/KitW-v mice to the development of 1, 2-dimethylhydrazine-induced intestinal tumors, 10.1038/labinvest.3700232
  27. Khan W. I., Richard M., Akiho H., Blennerhasset P. A., Humphreys N. E., Grencis R. K., Van Snick J., Collins S. M., Modulation of Intestinal Muscle Contraction by Interleukin-9 (IL-9) or IL-9 Neutralization: Correlation with Worm Expulsion in Murine Nematode Infections, 10.1128/iai.71.5.2430-2438.2003
  28. Razin E., Methods Enzymol., 187, 514 (1990)
  29. Saitoh Shinichiroh, Arudchandran Ramachandran, Manetz T.Scott, Zhang Weiguo, Sommers Connie L, Love Paul E, Rivera Juan, Samelson Lawrence E, LAT Is Essential for FcεRI-Mediated Mast Cell Activation, 10.1016/s1074-7613(00)80204-6
  30. Gondek D. C., Lu L.-F., Quezada S. A., Sakaguchi S., Noelle R. J., Cutting Edge: Contact-Mediated Suppression by CD4+CD25+ Regulatory Cells Involves a Granzyme B-Dependent, Perforin-Independent Mechanism, 10.4049/jimmunol.174.4.1783
Bibliographic reference LI, Li-Fan ; Lind, Evan F. ; Gondek, David C. ; Bennett, Kathy A. ; Gleeson, Michael W. ; et. al. Mast cells are essential intermediaries in regulatory T-cell tolerance. In: Nature : international weekly journal of science, Vol. 442, no. 7106, p. 997-1002 (2006)
Permanent URL http://hdl.handle.net/2078.1/38291