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Review
. 2014 Jun;35(6):233-42.
doi: 10.1016/j.it.2014.04.002. Epub 2014 Apr 28.

GATA3: a master of many trades in immune regulation

Yisong Y Wan  1
Affiliations
Review

GATA3: a master of many trades in immune regulation

Yisong Y Wan. Trends Immunol. 2014 Jun.

Abstract

GATA3 has conventionally been regarded as a transcription factor that drives the differentiation of T helper (Th) 2 cells. Increasing evidence points to a function for GATA3 beyond controlling Th2 differentiation. GATA3 regulates T cell development, proliferation, and maintenance. Furthermore, recent studies have demonstrated important roles for GATA3 in innate lymphoid cells. Thus, GATA3 emerges as a factor with diverse functions in immune regulation, which are in some cases cell-type specific and in others shared by multiple cell types. Here, I discuss recent discoveries and the current understanding of the functions of GATA3 in immune regulation.

Keywords: GATA3; T cell; Treg cell; innate lymphoid cell; natural killer T cell; natural killer cell.

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Figures

Figure 1
Figure 1. Th cell subsets and differentiation
Based on the signature cytokines produced, CD4+ helper T (Th) cells are classified as Th1, Th2, Th17 and Th9 cells. The differentiation of Th cells is induced by different combinations of cytokines and controlled by different transcription factors as depicted.
Figure 2
Figure 2. GATA3 integrates diverse upstream signals to control target gene expression and cellular functions
(A) GATA3 is regulated by multiple upstream signals. Signaling cascades activated through IL4 receptor (IL4R), IL2 receptor (IL2R), T cell receptor (TCR), Notch and Frizzled (receptor for Wnt) led to the activation of GATA3. p38 phosphorylates GATA3 to promote its nuclear translocation. GATA3 also activates its own expression through a feedback loop. Depending on the cellular and environmental contexts, one or more of these depicted signaling pathways control the functions of GATA3 in specific cell types. (B) GATA3 controls gene expression and cellular functions. As a transcription factor, GATA3 regulates target gene expression to control diverse cellular and biological processes. GATA3 activates TCRα and ThPOK expression during thymocyte development. It promotes Th2 cytokine expression to regulate Th1/Th2 cell differentiation, enhances Foxp3 expression to stabilize Treg cell function, and controls ROR-α expression for ILC2 generation. GATA3 is also required for the expression of Myc and IL7Rα that are critical for the metabolism, proliferation and homeostasis of immune cells. GATA3 achieves these diverse functions either by directly activating target genes or by associating with co-factors to regulate gene expression and the epigenetic modification.
Figure 3
Figure 3. GATA3 controls the generation and function of immune cells
During immune cell development and function, GATA3 plays positive (green plus symbol) or negative (red minus symbol) roles in different cell types. GATA3 is central for the development of multiple immune cell types: It controls the generation of early T cell progenitors, thymocytes, CD4+ T and iNKT (invariant natural killer T) cells. In contrast, GATA3 suppresses B cell development. GATA3 is also required for the development of NK (natural killer) and ILC2 (type-2 innate lymphoid cell) cells. In addition, GATA3 is critical for the function of various sub-types of mature T cells: While GATA3 promotes T cell homeostasis, activation, proliferation and the differentiation of Th2 and Th9 cells, it antagonizes Th1 and Th17 differentiation. Morevoer, GATA3 is required for Treg (regulatory T) cell homeostasis, suppressive activity and functional stability.
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