Ho IC, Tai TS, Pai SYGATA3 and the T-cell lineage: essential functions before and after T-helper-2-cell differentiation. Nat Rev Immunol 9:125-135

Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Nature Reviews Immunology (Impact Factor: 34.99). 02/2009; 9(2):125-35. DOI: 10.1038/nri2476
Source: PubMed


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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    • "Enhancing the Th1 and/or reducing the Th2 immune response to correct the Thl/Th2 imbalance may prevent allergic inflammatory reactions and ease the symptoms of allergic diseases (2–3,5,13–15). Regarding its important regulatory role in Th2 cell differentiation and Th2 cytokine secretion, GATA-3 is considered to be an important target for allergic diseases (7–8,10–12,14–15). "
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    ABSTRACT: Allergic rhinitis (AR) is primarily caused by a T helper cell (Th)1/Th2 imbalance. In a murine AR model of a previous study, the serum ovalbumin (OVA)-sIgE concentration was high, whereas microRNA (miR)-135a was lowly expressed in the nasal mucosa. The abnormal expression pattern of miR-135a coincided with highly expressed endogenous factors, including GATA binding protein (GATA)-3 and interleukin (IL)-4, and lowly expressed factors, including T-box expressed in T cells (T-bet) and interferon (IFN)-γ. We hypothesized that miR-135a may play an important role in immune regulation in AR mice. In the present study, AR was induced by OVA in the mice. Two groups of the AR mice were treated with a miR-135a mimic and a mimic control, respectively. The serum and nasal mucosa were collected for analysis. Following miR-135a application, the serum OVA-sIgE concentration was significantly reduced. In the nasal mucosa, the expression levels of miR-135a were higher, the mRNA and protein expression levels of GATA-3 and IL-4 were lower, and the expression levels of T-bet and IFN-γ were higher. The miR-135a corrected the Th1/Th2 imbalance in the AR mice. Findings of this study may provide a basis for novel genetic treatments in addressing allergic diseases.
    Full-text · Article · Oct 2014 · Experimental and therapeutic medicine
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    • "The secretion of IL-4 and IL-13 in the sera was also reduced in A. membranaceus–administered mice when compared with the saline-administered group (p < 0.05, Fig. 4C). These results suggest that the reduction in the total IgE level in the sera of allergic mice by A. membranaceus could result from the inhibition of IL-4 and IL-13. A. membranaceus reduces the level of GATA3 and increases the activity of PPAR␥ Because Th2 cytokines in allergic mice could be reduced by A. membranaceus administration, we hypothesized that the antiallergic effect of A. membranaceus may act through the regulation of transcriptional factors (i.e., T-bet and GATA-3) in Th1 and Th2 cell differentiation (Ho et al. 2009). To investigate the balance of Th2/ Th1, we determined that the ratio of GATA3/T-bet expression in lung tissues of allergic mice was reduced by administration of A. membranaceus (p < 0.05, Fig. 5A). "
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    ABSTRACT: Astragalus membranaceus, a traditional Chinese herb, has been used to improve airway inflammation and asthma. The present study investigated whether A. membranaceus has immunotherapeutic effects on asthma, a chronic inflammatory mucosal disease that is associated with excess production of IgE, eosinophilia, T helper 2 (Th2) cytokines, and bronchial hyperresponsiveness. An ovalbumin (OVA)-induced, chronic inflammatory airway murine asthma model was used to examine the status of pulmonary inflammation after the administration of A. membranaceus. The IgE levels in serum and bronchoalveolar lavage fluid showed a tendency to decrease after the administration of A. membranaceus. The number of eosinophils decreased and infiltration of inflammatory cells and collagen deposition declined in lung sections after A. membranaceus administration. The RNA and protein levels of Th2 cytokines and the ratio of the GATA3/T-bet mRNA levels decreased after A. membranaceus treatment. Furthermore, the mRNA level of peroxisome proliferator-activated receptor γ (PPARγ), a nuclear hormone receptor, increased in the lung tissues of A. membranaceus-treated mice. Finally, an A. membranaceus water extract activated PPARγ activity in either human embryonic kidney 293 (HEK293) or A549 cells in a PPARγ-responsive element-containing luciferase reporter assay. These results indicate that A. membranaceus has an inhibitory effect on airway inflammation in a murine model of asthma through modulating the imbalanced relationship between Th1 and Th2 cytokines.
    Full-text · Article · Sep 2014 · Biochemistry and Cell Biology
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    • "GATA-3 is the third member of the GATA family of transcription factors [1]. Among hematopoietic cells, GATA-3 is expressed nearly exclusively in the T lineage, and is critical for the development of CD4+ T helper (Th) cells [2], the differentiation of T helper type 2 (Th2) cells [3], [4], the function of regulatory T (Treg) cells [5], [6], and the activation/homeostasis of CD8+ cytolytic T (Tc) cells [7], [8]. "
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    ABSTRACT: The integral membrane protein 2a (Itm2a) is one of the BRICHOS domain-containing proteins and is structurally related to Itm2b and Itm2c. It is expressed preferentially in the T lineage among hematopoietic cells and is induced by MHC-mediated positive selection. However, its transcriptional regulation and function are poorly understood. Here we showed Itm2a to be a target gene of GATA-3, a T cell-specific transcription factor. Deficiency of Itm2a had little impact on the development and function of polyclonal T cells but resulted in a partial defect in the development of thymocytes bearing a MHC class I-restricted TCR, OT-I. In addition, Itm2a-deficient mice displayed an attenuated T helper cell-dependent immune response in vivo. We further demonstrated that Itm2b but not Itm2c was also expressed in T cells, and was induced upon activation, albeit following a kinetic different from that of Itm2a. Thus, functional redundancy between Itm2a and Itm2b may explain the minimal phenotype of Itm2a deficiency.
    Full-text · Article · May 2014 · PLoS ONE
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