GATA3 and the T-cell Lineage: Essential Functions Before and After T-helper-2-cell Differentiation

Overview

Journal Nat Rev Immunol

Specialty Allergy & Immunology

Date 2009 Jan 20

PMID 19151747

Citations 210

Authors

I-Cheng Ho

Tzong-Shyuan Tai

Sung-Yun Pai

Affiliations

Soon will be listed here.

Abstract

Many advances in our understanding of the molecules that regulate the development, differentiation and function of T cells have been made over the past few years. One important regulator of T-cell differentiation is the transcription factor GATA-binding protein 3 (GATA3). Although the main function of GATA3 is to act as a master transcription factor for the differentiation of T helper 2 (T(H)2) cells, new research has helped to uncover crucial functions of GATA3 in T cells that go beyond T(H)2-cell differentiation and that are important at earlier stages of haematopoietic and lymphoid-cell development. This Review focuses on the functions of GATA3 from early thymocyte development to effector T-cell differentiation. In addition, we discuss the interactions between GATA3 and other transcription factors and signalling pathways, and highlight the functional significance of the GATA3 protein structure.

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References

Reiner S . Development in motion: helper T cells at work. Cell. 2007; 129(1):33-6. DOI: 10.1016/j.cell.2007.03.019. View

Zhang D, Yang L, COHN L, Parkyn L, Homer R, Ray P . Inhibition of allergic inflammation in a murine model of asthma by expression of a dominant-negative mutant of GATA-3. Immunity. 1999; 11(4):473-82. DOI: 10.1016/s1074-7613(00)80122-3. View

Bender T, Kremer C, Kraus M, Buch T, Rajewsky K . Critical functions for c-Myb at three checkpoints during thymocyte development. Nat Immunol. 2004; 5(7):721-9. DOI: 10.1038/ni1085. View

Egawa T, Littman D . ThPOK acts late in specification of the helper T cell lineage and suppresses Runx-mediated commitment to the cytotoxic T cell lineage. Nat Immunol. 2008; 9(10):1131-9. PMC: 2666788. DOI: 10.1038/ni.1652. View

Nawijn M, Ferreira R, Dingjan G, Kahre O, Drabek D, Karis A . Enforced expression of GATA-3 during T cell development inhibits maturation of CD8 single-positive cells and induces thymic lymphoma in transgenic mice. J Immunol. 2001; 167(2):715-23. DOI: 10.4049/jimmunol.167.2.715. View

Pandolfi P, Roth M, Karis A, Leonard M, Dzierzak E, Grosveld F . Targeted disruption of the GATA3 gene causes severe abnormalities in the nervous system and in fetal liver haematopoiesis. Nat Genet. 1995; 11(1):40-4. DOI: 10.1038/ng0995-40. View

Aliahmad P, Kaye J . Commitment issues: linking positive selection signals and lineage diversification in the thymus. Immunol Rev. 2006; 209:253-73. DOI: 10.1111/j.0105-2896.2006.00345.x. View

Hendriks R, Nawijn M, Engel J, van Doorninck H, Grosveld F, Karis A . Expression of the transcription factor GATA-3 is required for the development of the earliest T cell progenitors and correlates with stages of cellular proliferation in the thymus. Eur J Immunol. 1999; 29(6):1912-8. DOI: 10.1002/(SICI)1521-4141(199906)29:06<1912::AID-IMMU1912>3.0.CO;2-D. View

Ouyang W, Ranganath S, Weindel K, Bhattacharya D, MURPHY T, Sha W . Inhibition of Th1 development mediated by GATA-3 through an IL-4-independent mechanism. Immunity. 1998; 9(5):745-55. DOI: 10.1016/s1074-7613(00)80671-8. View

10.

Dong C . TH17 cells in development: an updated view of their molecular identity and genetic programming. Nat Rev Immunol. 2008; 8(5):337-48. DOI: 10.1038/nri2295. View

11.

Lucas B, Germain R . Unexpectedly complex regulation of CD4/CD8 coreceptor expression supports a revised model for CD4+CD8+ thymocyte differentiation. Immunity. 1996; 5(5):461-77. DOI: 10.1016/s1074-7613(00)80502-6. View

12.

Zhu J, Cote-Sierra J, Guo L, Paul W . Stat5 activation plays a critical role in Th2 differentiation. Immunity. 2003; 19(5):739-48. DOI: 10.1016/s1074-7613(03)00292-9. View

13.

Shimoda K, van Deursen J, Sangster M, Sarawar S, Carson R, Tripp R . Lack of IL-4-induced Th2 response and IgE class switching in mice with disrupted Stat6 gene. Nature. 1996; 380(6575):630-3. DOI: 10.1038/380630a0. View

14.

He X, He X, Dave V, Zhang Y, Hua X, Nicolas E . The zinc finger transcription factor Th-POK regulates CD4 versus CD8 T-cell lineage commitment. Nature. 2005; 433(7028):826-33. DOI: 10.1038/nature03338. View

15.

Kaplan M, Schindler U, Smiley S, Grusby M . Stat6 is required for mediating responses to IL-4 and for development of Th2 cells. Immunity. 1996; 4(3):313-9. DOI: 10.1016/s1074-7613(00)80439-2. View

16.

He X, Park K, Wang H, He X, Zhang Y, Hua X . CD4-CD8 lineage commitment is regulated by a silencer element at the ThPOK transcription-factor locus. Immunity. 2008; 28(3):346-58. DOI: 10.1016/j.immuni.2008.02.006. View

17.

Hedrick S . T cell development: bottoms-up. Immunity. 2002; 16(5):619-22. DOI: 10.1016/s1074-7613(02)00316-3. View

18.

Lee H, Takemoto N, Kurata H, Kamogawa Y, Miyatake S, OGarra A . GATA-3 induces T helper cell type 2 (Th2) cytokine expression and chromatin remodeling in committed Th1 cells. J Exp Med. 2000; 192(1):105-15. PMC: 1887713. DOI: 10.1084/jem.192.1.105. View

19.

Ting C, Olson M, Barton K, Leiden J . Transcription factor GATA-3 is required for development of the T-cell lineage. Nature. 1996; 384(6608):474-8. DOI: 10.1038/384474a0. View

20.

Amsen D, Antov A, Flavell R . The different faces of Notch in T-helper-cell differentiation. Nat Rev Immunol. 2009; 9(2):116-24. DOI: 10.1038/nri2488. View