GATA-3 - not just for Th2 cells anymore

Harvard University, Cambridge, Massachusetts, United States
Cellular & molecular immunology (Impact Factor: 4.11). 03/2007; 4(1):15-29.
Source: PubMed


GATA-3 was first cloned as a T cell specific transcription factor in 1991 and its importance in the transcriptional control of T helper type 2 cell (Th2) differentiation was established in the mid to late 90's. A role for GATA-3 during thymic development has long implied by its continuous and regulated expression through out T lineage development, but the absolute requirement for GATA-3 during early T lymphoid commitment/survival previously precluded definitive answers to this question. Several technical breakthroughs have fueled fruitful investigation in recent years and uncovered unexpected and critical roles for GATA-3 in CD4 thymocyte survival, invariant natural killer T cell generation and function, and also in beta selection. Not only does GATA-3 participate in nearly every stage of T cell development from common lymphoid progenitor to Th2, conditional knockout studies have indicated that the influence of GATA-3 also extends beyond the immune system.

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Available from: Sung-Yun Pai
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    • "However, the expression and function of GATA and Sp1 factors in helper T lymphocytes (Th cells, CD4+ lymphocytes) is still poorly understood. GATA3 is considered to be the only GATA member that is expressed in CD4+ lymphocytes (reviewed in [12]). The transcriptional activity of Sp1 has been described in proliferating T lymphocytes and is presumably involved in cell cycle regulation [19]. "
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    • "This phenotype is representative of the basal subtype of tumors, which are negative for ER and HER2 expression. In breast, GATA-3 plays an important role in mammary gland development and differentiation (Bossard and Zaret 1998; Ho and Pai 2007). Moreover, the inactivation of GATA-3 in mice results in contracted mammary epithelial structure, severely impaired lactogenesis, and disrupted differentiation of luminal progenitor cells into ductal and alveolar cells (Asselin-Labat et al. 2007). "
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    • "GATA-3 plays at least three roles in T cell development: during initial specification, during TCRαβ-dependent positive selection, and in mature T cells where it establishes the Th2 effector program. In the Th2 context the addition of GATA-3 clearly promotes Th2 fate just as loss of GATA-3 inhibits it [23] [24]. In TCRαβ-mediated positive selection of CD4 + lineage thymocytes its effects can be more complicated, but again the gain of function of GATA-3 promotes the CD4 + fate relative to other options [25] [26] [27]. "
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