| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,
* Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Brigham and Women’s Hospital, Boston, MA 02115;
Harvard Medical School, Boston, MA 02115;
Division of Hematology/Oncology, Children’s Hospital Boston and Department of Pediatric Oncology, Dana-Farber Cancer Institute;
School of Biosciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom; and
¶ Department of Medical Microbiology and Immunology, University of Wisconsin-Madison Medical School, Madison, WI 53706
Although invariant NKT (iNKT) cells participate in many aspects of immune responses, the molecular mechanisms regulating their development, maturation, and activation are still poorly understood. GATA-3 is a T cell-specific transcription factor that is also expressed in iNKT cells. The critical role of GATA-3 in conventional 
β T cells has been well documented, but whether GATA-3 also regulates the development and function of iNKT cells is unknown. In the present study, we report that deficiency of GATA-3 results in cell-intrinsic defects in the thymic development and peripheral maturation of murine iNKT cells. In addition, GATA-3 is also required for survival, activation, and effector functions of this unique population of T cells. Our data also reveal a previously unidentified peripheral maturation step that is GATA-3 dependent.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This research was made possible by grants from the National Institutes of Health (Rheumatology Fellowship Training Grant (to P.J.K.), K08-AI050601 (to S.-Y.P.), and R01-AI054451 (to I.-C.H.)), American College of Rheumatology-Physician Scientist Development Award (to P.J.K.), Lister Institute-Jenner Research Fellowship (to G.S.B.), Medical Research Council (to G.S.B.), and The Wellcome Trust (to G.S.B.).
2 Address correspondence and reprint requests to Dr. I-Cheng Ho, One Jimmy Fund Way, Smith Building, Room 524, Boston, MA 02115. E-mail address: iho{at}partners.org
3 Abbreviations used in this paper: iNKT, invariant NKT; 7-AAD, 7-aminoactinomycin D; DN, double negative; DP, double positive; GalCer, -galactosylceramide; KO, knockout; MFI, mean fluorescence intensity; PKC, protein kinase C; qPCR, quantitative PCR; SP, single positive; WT, wild type.
This article has been cited by other articles:
|
|
 |
|
  L. Zhou, K.-H. Seo, H.-Z. He, R. Pacholczyk, D.-M. Meng, C.-G. Li, J. Xu, J.-X. She, Z. Dong, and Q.-S. Mi Tie2cre-induced inactivation of the miRNA-processing enzyme Dicer disrupts invariant NKT cell development PNAS, June 23, 2009; 106(25): 10266 - 10271. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Cen, A. Ueda, L. Guzman, J. Jain, H. Bassiri, K. E. Nichols, and P. L. Stein The Adaptor Molecule Signaling Lymphocytic Activation Molecule-Associated Protein (SAP) Regulates IFN-{gamma} and IL-4 Production in V{alpha}14 Transgenic NKT Cells via Effects on GATA-3 and T-bet Expression J. Immunol., February 1, 2009; 182(3): 1370 - 1378. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Diao, K. Iwabuchi, L. Li, K. Onoe, L. Van Kaer, S. Kon, Y. Saito, J. Morimoto, D. T. Denhardt, S. Rittling, et al. Osteopontin regulates development and function of invariant natural killer T cells PNAS, October 14, 2008; 105(41): 15884 - 15889. [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]
|
|
|
|
|
|
M. Felices and L. J. Berg The Tec Kinases Itk and Rlk Regulate NKT Cell Maturation, Cytokine Production, and Survival J. Immunol., March 1, 2008; 180(5): 3007 - 3018. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Aliahmad and J. Kaye Development of all CD4 T lineages requires nuclear factor TOX J. Exp. Med., January 21, 2008; 205(1): 245 - 256. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Wesley, M. S. Tessmer, C. Paget, F. Trottein, and L. Brossay A Y Chromosome-Linked Factor Impairs NK T Development J. Immunol., September 15, 2007; 179(6): 3480 - 3487. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
