| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Department of Immunology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304; and
Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60634
The commitment of naive T cells to polarized Th cells requires
specific changes in their transcription factors. Retrovirally
overexpressed GATA-3 has been reported to induce the Th2 cytokine
profile in developing Th1 cells. In this study, we examined the role of
the N-terminal finger (Nf) of GATA-3 in Th2 cell development. The Nf,
as well as the C-terminal finger and the transactivation domain, is
critical for the induction of the Th2 phenotype. Using the GATA-3-Nf as
a bait, our yeast two-hybrid screening identified friend of GATA (FOG)
in the Th2 cell-specific library. Naive T cells express significant
levels of FOG mRNA, which was rapidly down-regulated upon commitment to
both Th1 and Th2 lineages. In reporter assays, FOG blocked the
GATA-3-mediated activation of several cytokine promoters. Finally,
retroviral expression of FOG in developing Th2 cells suppressed both
IL-4 and IL-5 and allowed for IFN-
production, which was accompanied
by a significant level of T-bet mRNA expression. Serial deletion
mutation analysis indicated that the N-terminal region, but not the
consensus C-terminal binding protein-binding motif, of FOG is critical
for the effects. Our results clearly indicate that 1) FOG is a
repressor of GATA-3 in naive T cells and 2) the down-regulation of FOG
induces Th2 cell differentiation by releasing GATA-3 from its
repression.
This article has been cited by other articles:
|
|
 |
|
  X. Zhao, B. Zheng, Y. Huang, D. Yang, S. Katzman, C. Chang, D. Fowell, and W.-p. Zeng Interaction between GATA-3 and the Transcriptional Coregulator Pias1 Is Important for the Regulation of Th2 Immune Responses J. Immunol., December 15, 2007; 179(12): 8297 - 8304. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Nakano, H. Hosokawa, M. Kohyama, and N. Hozumi NF-AT-Mediated Expression of TGF-beta1 in Tolerant T Cells J. Immunol., March 1, 2007; 178(5): 3067 - 3075. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Jenks, B. J. Eisfelder, and J. Miller LFA-1 co-stimulation inhibits Th2 differentiation by down-modulating IL-4 responsiveness Int. Immunol., March 1, 2005; 17(3): 315 - 323. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Balmelle, N. Zamarreno, M. S. Krangel, and C. Hernandez-Munain Developmental Activation of the TCR {alpha} Enhancer Requires Functional Collaboration among Proteins Bound Inside and Outside the Core Enhancer J. Immunol., October 15, 2004; 173(8): 5054 - 5063. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Savignac, B. Gomes, A. Gallard, S. Narbonnet, M. Moreau, C. Leclerc, P. Paulet, B. Mariame, P. Druet, A. Saoudi, et al. Dihydropyridine Receptors Are Selective Markers of Th2 Cells and Can Be Targeted to Prevent Th2-Dependent Immunopathological Disorders J. Immunol., May 1, 2004; 172(9): 5206 - 5212. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Sundrud, S. M. Grill, D. Ni, K. Nagata, S. S. Alkan, A. Subramaniam, and D. Unutmaz Genetic Reprogramming of Primary Human T Cells Reveals Functional Plasticity in Th Cell Differentiation J. Immunol., October 1, 2003; 171(7): 3542 - 3549. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. K. Kaufman, P. Zhou, H. A. Pasolli, M. Rendl, D. Bolotin, K.-C. Lim, X. Dai, M.-L. Alegre, and E. Fuchs GATA-3: an unexpected regulator of cell lineage determination in skin Genes & Dev., September 1, 2003; 17(17): 2108 - 2122. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Takemoto, K.-i. Arai, and S. Miyatake Cutting Edge: The Differential Involvement of the N-Finger of GATA-3 in Chromatin Remodeling and Transactivation During Th2 Development J. Immunol., October 15, 2002; 169(8): 4103 - 4107. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
