International Immunology Advance Access originally published online on July 6, 2005
International Immunology 2005 17(8):993-1007; doi:10.1093/intimm/dxh281
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Asthmatic changes in mice lacking T-bet are mediated by IL-13
1 Laboratory of Cellular and Molecular Immunology of the Lung and 2 Pathology Department, University of Mainz, Mainz, Germany
3 Department of Immunology and Infections Diseases, Harvard School of Public Health and 4 Department of Medicine, Harvard Medical School, Boston, MA, USA
Correspondence to: L. H. Glimcher; E-mail: lglimche{at}hsph.harvard.edu or S. Finotto; E-mail: finotto{at}mail.uni-mainz.de
Mice with a targeted deletion of the T-bet gene exhibit spontaneous airway hyperresponsiveness (AHR), airway inflammation, enhanced recovery of Th2 cytokines from bronchoalveolar lavage fluid, sub-epithelial collagen deposition and myofibroblast transformation. Here we analyze the mechanisms responsible for the chronic airway remodeling observed in these mice. CD4+ T cells isolated from the lung of T-bet-deficient mice were spontaneously activated CD44highCD69high memory T cells, with a typical Th2 cytokine profile. Neutralization of IL-13 but not IL-4 resulted in amelioration of AHR in airways of mice lacking T-bet. IL-13 blockade also led to reduced eosinophilia and decreased vimentin, transforming growth factor beta (TGF-ß) and alpha smooth muscle actin (
SMA) levels. T-bet–/– lung fibroblasts proliferated very rapidly and released increased amounts of TGF-ß. Interestingly, neutralization of TGF-ß ameliorated aspects of the chronic airway remodeling phenotype but did not reduce AHR. These data highlight a T-bet-directed function for IL-13 in controlling lung remodeling that is both dependent on and independent of its interaction with TGF-ß in the asthmatic airway.
Keywords: airway remodeling, asthma, cytokines, T-bet, TGF-ß
Transmitting editor: A. Singer
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  H. Y. Kim, M. Pichavant, P. Matangkasombut, Y. I. Koh, P. B. Savage, R. H. DeKruyff, and D. T. Umetsu The Development of Airway Hyperreactivity in T-bet-Deficient Mice Requires CD1d-Restricted NKT Cells J. Immunol., March 1, 2009; 182(5): 3252 - 3261. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. A. Dolgachev, M. R. Ullenbruch, N. W. Lukacs, and S. H. Phan Role of Stem Cell Factor and Bone Marrow-Derived Fibroblasts in Airway Remodeling Am. J. Pathol., February 1, 2009; 174(2): 390 - 400. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Doganci, R. Karwot, J. H. Maxeiner, P. Scholtes, E. Schmitt, M. F. Neurath, H. A. Lehr, I-C. Ho, and S. Finotto IL-2 Receptor {beta}-Chain Signaling Controls Immunosuppressive CD4+ T Cells in the Draining Lymph Nodes and Lung during Allergic Airway Inflammation In Vivo J. Immunol., August 1, 2008; 181(3): 1917 - 1926. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Joetham, S. Matsubara, M. Okamoto, K. Takeda, N. Miyahara, A. Dakhama, and E. W. Gelfand Plasticity of Regulatory T Cells: Subversion of Suppressive Function and Conversion to Enhancement of Lung Allergic Responses J. Immunol., June 1, 2008; 180(11): 7117 - 7124. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Sehra, H. A. Bruns, A.-N. N. Ahyi, E. T. Nguyen, N. W. Schmidt, E. G. Michels, G.-U. von Bulow, and M. H. Kaplan IL-4 Is a Critical Determinant in the Generation of Allergic Inflammation Initiated by a Constitutively Active Stat6 J. Immunol., March 1, 2008; 180(5): 3551 - 3559. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. G. Martin and T. Jo Genetic Differences in Airway Smooth Muscle Function Proceedings of the ATS, January 1, 2008; 5(1): 73 - 79. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. O. Aliprantis, J. Wang, J. W. Fathman, R. Lemaire, D. M. Dorfman, R. Lafyatis, and L. H. Glimcher Transcription factor T-bet regulates skin sclerosis through its function in innate immunity and via IL-13 PNAS, February 20, 2007; 104(8): 2827 - 2830. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. D. Fixman, A. Stewart, and J. G. Martin Basic mechanisms of development of airway structural changes in asthma Eur. Respir. J., February 1, 2007; 29(2): 379 - 389. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Xu, A. L. Mora, J. LaVoy, K. L. Brigham, and M. Rojas Increased bleomycin-induced lung injury in mice deficient in the transcription factor T-bet Am J Physiol Lung Cell Mol Physiol, October 1, 2006; 291(4): L658 - L667. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. S. Bakshi, M. Malik, P. M. Carrico, and T. J. Sellati T-bet Deficiency Facilitates Airway Colonization by Mycoplasma pulmonis in a Murine Model of Asthma J. Immunol., August 1, 2006; 177(3): 1786 - 1795. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kimura, Y. Ishii, K. Yoh, Y. Morishima, T. Iizuka, T. Kiwamoto, Y. Matsuno, S. Homma, A. Nomura, T. Sakamoto, et al. Overexpression of the Transcription Factor GATA-3 Enhances the Development of Pulmonary Fibrosis Am. J. Pathol., July 1, 2006; 169(1): 96 - 104. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. A. Raby, E.-S. Hwang, K. V. Steen, K. Tantisira, S. Peng, A. Litonjua, R. Lazarus, C. Giallourakis, J. D. Rioux, D. Sparrow, et al. T-Bet Polymorphisms Are Associated with Asthma and Airway Hyperresponsiveness Am. J. Respir. Crit. Care Med., January 1, 2006; 173(1): 64 - 70. [Abstract] [Full Text] [PDF]
|
|