T cell factor 1 initiates the T helper type 2 fate by inducing the transcription factor GATA-3 and repressing interferon-γ

Yu, Qing; Sharma, Archna; Oh, Sun Young; Moon, Hyung‐Geun; Hossain, Zulfiquer M.; Salay, Theresa M.; Leeds, Karen E.; Du, Huarui; Wu, Beibei; Waterman, Marian L.; Zhu, Zhou; Sen, Jyoti Misra

doi:10.1038/ni.1762

Cited by 189 publications

(232 citation statements)

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“…T-bet, a member of the T-box family of transcription factors, has been demonstrated to be involved in polarization toward Th1 cells, while GATA-3 has been demonstrated to be involved in Th2 differentiation (30,31). To further confirm the association between Th1 and Th2 in HBV transgenic mice, real-time PCR and western blot analysis were performed on T cells to assess the expression of T-bet and GATA-3 in the various treatment groups.…”

Section: Discussionmentioning

confidence: 99%

Fusion protein of tapasin and hepatitis B core antigen 18-27 enhances T helper cell type 1/2 cytokine ratio and antiviral immunity by inhibiting suppressors of cytokine signaling family members 1/3 in hepatitis B virus transgenic mice

Tang

Chen

Zhang

et al. 2014

Molecular Medicine Reports

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Abstract. Persistent hepatitis B virus (HBV) infection ischaracterized by a weak adaptive immune response, which is considered to be due to an imbalance of T helper cell types 1 and 2 (Th1/Th2). Suppressors of cytokine signaling (SOCS) family members, particularly SOCS1 and SOCS3, have been demonstrated to be important in the regulation of T cell differentiation. Previous studies by our group showed that the expressed and purified fusion protein of cytoplasmic transduction peptide (CTP) and HBV core antigen 18-27 (HBcAg18-27)-tapasin was able to enter the cytoplasm of bone marrow-derived dendritic cells (BMDCs), promoting the maturation of BMDCs and efficiently enhancing T cell immune responses in vitro. In the present study, HBcAg-specific immune responses induced by CTP-HBcAg18-27-tapasin in HBV were assessed in transgenic mice, and SOCS1 and SOCS3 were identified as negative regulators of this response. The Th1/Th2 cytokine ratio was analyzed by ELISA. The expression of T cell-specific T-box transcription factor (T-bet) and GATA-binding protein 3 (GATA-3), SOCS1 and SOCS3 were detected by real-time quantitative polymerase chain reaction and western blot analysis. The results demonstrated that CTP-HBcAg18-27-tapasin significantly increased the Th1/Th2 cytokine ratio in HBV transgenic mice. CTP-HBcAg18-27-tapasin immunization more efficiently suppressed the expression of serum hepatitis B surface antigen (HBsAg), HBV DNA as well as liver HBsAg and HBcAg in HBV transgenic mice. Furthermore, CTP-HBcAg18-27-tapasin promotes T-bet but reduces GATA-3 expression. In addition, the expression of SOCS1 and SOCS3 was significantly downregulated in the CTP-HBcAg18-27-tapasin group compared with the control groups. In conclusion, the present study demonstrated that CTP-HBcAg18-27-tapasin enhanced the Th1/Th2 cytokine ratio and antiviral immunity by suppressing SOCS1/3 in HBV transgenic mice.

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Section: Discussionmentioning

confidence: 99%

Fusion protein of tapasin and hepatitis B core antigen 18-27 enhances T helper cell type 1/2 cytokine ratio and antiviral immunity by inhibiting suppressors of cytokine signaling family members 1/3 in hepatitis B virus transgenic mice

Tang

Chen

Zhang

et al. 2014

Molecular Medicine Reports

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“…All qRT-PCR experiments were performed by using the total RT product from 100 cell equivalents, and results were quantified relative to the mRNA expression levels of the hypoxanthine phosphoribosyltransferase (HPRT) and ␤-actin endogenous reference genes. Primers used in this study included primers described previously for GATA3 (76), E47 (77), HPRT (78), and ACTB (79); forward primer 5=-CAAGGTAGCTTAGCCA ACATGG-3= and reverse primer 5=-GTGGGTGTTGAATTTCATCGGG-3= for RAG1; forward primer 5=-AGTAT TTCACATCCACAAGCAGG-3= and reverse primer 5=-TGACCCACTGTTACCATCTGC-3= for RAG2; forward primer 5=-GGGAATCTTCGACAGCCAGG-3= and reverse primer 5=-AGTTTGAAGAGGAGCAGGCG-3= for PTCRA; forward primer 5=-AGCAGCACTGTGTGCCCTGG-3= and reverse primer 5=-TCTGGGTAGGTAGGGTT GGCTCC-3= for ETS1; forward primer 5=-TTTTGGTGGGTGTTCTTGGC-3= and reverse primer 5=-ACATTGCA TCAGAGACTTGGC-3= for ATM; and forward primer 5=-GAGCCTCCTACTTCCAGTGC-3= and reverse primer 5=-GAAGACATCCTCCTCGCAGC-3= for CCND3.…”

Section: Methodsmentioning

confidence: 99%

GATA3 Abundance Is a Critical Determinant of T Cell Receptor β Allelic Exclusion

Sekiguchi

Panwar

et al. 2017

Molecular and Cellular Biology

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Allelic exclusion describes the essential immunological process by which feedback repression of sequential DNA rearrangements ensures that only one autosome expresses a functional T or B cell receptor. In wild-type mammals, approximately 60% of cells have recombined the DNA of one T cell receptor ␤ (TCR␤) V-to-DJ-joined allele in a functional configuration, while the second allele has recombined only the DJ sequences; the other 40% of cells have recombined the V to the DJ segments on both alleles, with only one of the two alleles predicting a functional TCR␤ protein. Here we report that the transgenic overexpression of GATA3 leads predominantly to biallelic TCR␤ gene (Tcrb) recombination. We also found that wild-type immature thymocytes can be separated into distinct populations based on intracellular GATA3 expression and that GATA3 LO cells had almost exclusively recombined only one Tcrb locus (that predicted a functional receptor sequence), while GATA3 HI cells had uniformly recombined both Tcrb alleles (one predicting a functional and the other predicting a nonfunctional rearrangement). These data show that GATA3 abundance regulates the recombination propensity at the Tcrb locus and provide new mechanistic insight into the historic immunological conundrum for how Tcrb allelic exclusion is mediated.KEYWORDS allelic exclusion, T cell receptor beta locus, GATA3, monoallelic-tobiallelic switch O ne enduring mystery in cellular immunology regards the underlying mechanisms that control antigen receptor allelic exclusion (1, 2), the process whereby B or T lymphocytes are programmed to express only one functional allele for each chain of their respective antigen receptors (B cell receptor [BCR] or T cell receptor [TCR]), thus avoiding the coexistence of multiple antigen specificities in a single immune cell. Lymphocytes acquire the diversity of antigen recognition (3) as well as a unique monospecificity for particular antigens (4) during development in the bone marrow (B cells) or the thymus (T cells).T lymphocyte development is generally characterized by division into multiple stages based on developmental timing and the location and expression of specific cell surface markers (5). T cell development begins when multipotential hematopoietic progenitor cells in the bone marrow migrate through the bloodstream to the thymus, where early T lineage progenitors (ETPs) are generated and later specified to become T cells (6-10). ETPs differentiate into double-negative (DN) cells (DN2 to DN4 stages) that express neither the CD4 nor the CD8 coreceptor, then into double-positive (DP)

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“…Previous work has demonstrated that GATA3 can be induced in conventional CD4 + T cells following TCR stimulation (38)(39)(40). To assess whether a similar mechanism could account for GATA3 expression by Tregs, highly purified Foxp3 + CD4 + T cells were cocultured with splenic DCs (SpDCs) in the presence of anti-CD3 antibody.…”

Section: Figurementioning

confidence: 99%

GATA3 controls Foxp3+ regulatory T cell fate during inflammation in mice

et al. 2011

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Tregs not only keep immune responses to autoantigens in check, but also restrain those directed toward pathogens and the commensal microbiota. Control of peripheral immune homeostasis by Tregs relies on their capacity to accumulate at inflamed sites and appropriately adapt to their local environment. To date, the factors involved in the control of these aspects of Treg physiology remain poorly understood. Here, we show that the canonical Th2 transcription factor GATA3 is selectively expressed in Tregs residing in barrier sites including the gastrointestinal tract and the skin. GATA3 expression in both murine and human Tregs was induced upon TCR and IL-2 stimulation. Although GATA3 was not required to sustain Treg homeostasis and function at steady state, GATA3 played a cardinal role in Treg physiology during inflammation. Indeed, the intrinsic expression of GATA3 by Tregs was required for their ability to accumulate at inflamed sites and to maintain high levels of Foxp3 expression in various polarized or inflammatory settings. Furthermore, our data indicate that GATA3 limits Treg polarization toward an effector T cell phenotype and acquisition of effector cytokines in inflamed tissues. Overall, our work reveals what we believe to be a new facet in the complex role of GATA3 in T cells and highlights what may be a fundamental role in controlling Treg physiology during inflammation.

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T cell factor 1 initiates the T helper type 2 fate by inducing the transcription factor GATA-3 and repressing interferon-γ

Cited by 189 publications

References 49 publications

Fusion protein of tapasin and hepatitis B core antigen 18-27 enhances T helper cell type 1/2 cytokine ratio and antiviral immunity by inhibiting suppressors of cytokine signaling family members 1/3 in hepatitis B virus transgenic mice

Fusion protein of tapasin and hepatitis B core antigen 18-27 enhances T helper cell type 1/2 cytokine ratio and antiviral immunity by inhibiting suppressors of cytokine signaling family members 1/3 in hepatitis B virus transgenic mice

GATA3 Abundance Is a Critical Determinant of T Cell Receptor β Allelic Exclusion

GATA3 controls Foxp3+ regulatory T cell fate during inflammation in mice

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