GATA3: a master of many trades in immune regulation

Wan, Yisong Y.

doi:10.1016/j.it.2014.04.002

Cited by 180 publications

(146 citation statements)

References 116 publications

(177 reference statements)

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“…We also observed frequent expression of GATA3 and BCL6 , though the relationship to function is not directly evident, as they have multiple effects on T cell function. GATA3 is associated with driving CD4 + Th2 responses, but is also involved in T cell homeostasis and Th9 differentiation [38]. BCL6 is associated with differentiation of follicular helper T cells, which have recently been identified as having a role in antibody-mediated cGVHD [39,40], and is also associated with multiple other effects, including CD8 + T cell proliferative burst and promoting memory T cell development [41–43].…”

Section: Discussionmentioning

confidence: 99%

Proinflammatory Dual Receptor T Cells in Chronic Graft-versus-Host Disease

Balakrishnan

Gloude

Šášik

et al. 2017

Biology of Blood and Marrow Transplantation

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Defective post-transplantation thymopoiesis is associated with chronic graft-versus-host disease (GVHD), a multiorgan pathology affecting up to 80% of patients after allogeneic hematopoietic stem cell transplantation (HSCT). Previous work demonstrated that the subset of T cells expressing 2 T cell receptors (TCRs) is predisposed to alloreactivity, driving selective and disproportionate activity in acute GVHD in both mouse models and HSCT patients. Here we investigate a potential role for this pathogenic T cell subset in chronic GVHD (cGVHD). HSCT patients with cGVHD demonstrated increased numbers of dual TCR cells in circulation. These dual receptor cells had an activated phenotype, indicating an active role in cGVHD. Notably, single-cell RNA sequencing identified the increased dual TCR cells in cGVHD as predominantly expressing Tbet, indicative of a proinflammatory phenotype. These results identify dual TCR cells as specific mediators of pathogenic inflammation underlying cGVHD and highlight Tbet-driven T cell function as a potential pathway for potential therapeutic targeting.

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Section: Discussionmentioning

confidence: 99%

Proinflammatory Dual Receptor T Cells in Chronic Graft-versus-Host Disease

Balakrishnan

Gloude

Šášik

et al. 2017

Biology of Blood and Marrow Transplantation

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“…In the early sepsis stage, TCR trigger GATA-3 upregulation via PI3K-mTOR dependent pathways [41]. Moreover, GATA-3 is suggested to mediate notch signaling that is important for promoting T cell development and proliferation [42].…”

Section: Discussionmentioning

confidence: 99%

Interaction between ANXA1 and GATA-3 in Immunosuppression of CD4⁺ T Cells

Huang

Zhou

Liu

et al. 2016

Mediators of Inflammation

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Decreased Th1/Th2 ratio is one of the major characteristics of immunosuppression in sepsis. Both membrane adhesive protein Annexin-A1 (ANXA1) and transcription factor GATA-3 have been reported to play important roles in T cell differentiation. However, the relationship between ANXA1 and GATA-3 in Th1/Th2 shift is unknown. Our study investigated the interaction effects of ANXA1 and GATA-3 to influence T cell differentiation in CD4+ T cells. We found that GATA-3 and ANXA1 were coexpressed on Th0/Th1/Th2 cytoplasm and nuclear. Overexpressed ANXA1 significantly increased the expression of IFNγ and reduced IL-4 expression in T cells, while ANXA1-silenced T cells exhibited decreased production of IFNγ and increased production of IL-4. Knockdown of ANXA1 promoted higher expression level of GATA-3 and low level of T-box transcription factor (T-bet/Tbx21). Further study demonstrated that ANXA1 regulated GATA-3 expression through the formyl peptide receptor like-1 (FPRL-1) downstream signaling pathways ERK and PKB/Akt. These results suggested that ANXA1 modulates GATA-3/T-bet expression induced Th0/Th1 differentiation. Moreover, we found that GATA-3 inhibited ANXA1 expression by binding to its promoter for the first time. It is proposed that the interactions between ANXA1 and GATA-3 may provide clues to understand the immunosuppression and have potential as new therapeutic targets in immunotherapy after sepsis.

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“…GATA3 is known to play crucial roles in a variety of immune cells in a developmental stage-and cell-lineage-specific fashion (27). For instance, GATA3 is important in the development and maintenance of T cells (27)(28)(29). Notably, GATA3 plays a critical role in the differentiation of Th2 cells and their ability to secrete cytokines such as IL-4, IL-5, and IL-13.…”

mentioning

confidence: 99%

NK Cell–Specific Gata3 Ablation Identifies the Maturation Program Required for Bone Marrow Exit and Control of Proliferation

Ali

Vivier

et al. 2016

The Journal of Immunology

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NK cells are innate lymphocytes capable of eliciting an innate immune response to pathogens. NK cells develop and become mature in the bone marrow (BM) before they migrate out to peripheral organs. Although the developmental program leading to mature NK cells has been studied in the context of several transcription factors, the stage-specific role of GATA3 in NK cell development has been incompletely understood. Using NKp46-Cre-Gata3fl/fl mice in which Gata3 deficiency was induced as early as the immature stage of NK cell differentiation, we demonstrated that GATA3 is required for the NK cell maturation beyond the CD27 single-positive stage and is indispensable for the maintenance of liver-resident NK cells. The frequencies of NK cells from NKp46-Cre-Gata3fl/fl mice were found higher in the BM but lower in peripheral organs compared with control littermates, indicating that GATA3 controls the maturation program required for BM egress. Despite the defect in maturation, upon murine CMV infection, NK cells from NKp46-Cre-Gata3fl/fl mice expanded vigorously, achieving NK cell frequencies surpassing those in controls and therefore provided comparable protection. The heightened proliferation of NK cells from NKp46-Cre-Gata3fl/fl mice was cell intrinsic and associated with enhanced upregulation of CD25 expression. Taken together, our results demonstrate that GATA3 is a critical regulator for NK cell terminal maturation and egress out of the BM and that immature NK cells present in the periphery of NKp46-Cre-Gata3fl/fl mice can rapidly expand and provide a reservoir of NK cells capable of mounting an efficient cytotoxic response upon virus infection.

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GATA3: a master of many trades in immune regulation

Cited by 180 publications

References 116 publications

Proinflammatory Dual Receptor T Cells in Chronic Graft-versus-Host Disease

Proinflammatory Dual Receptor T Cells in Chronic Graft-versus-Host Disease

Interaction between ANXA1 and GATA-3 in Immunosuppression of CD4⁺ T Cells

NK Cell–Specific Gata3 Ablation Identifies the Maturation Program Required for Bone Marrow Exit and Control of Proliferation

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GATA3: a master of many trades in immune regulation

Cited by 180 publications

References 116 publications

Proinflammatory Dual Receptor T Cells in Chronic Graft-versus-Host Disease

Proinflammatory Dual Receptor T Cells in Chronic Graft-versus-Host Disease

Interaction between ANXA1 and GATA-3 in Immunosuppression of CD4+ T Cells

NK Cell–Specific Gata3 Ablation Identifies the Maturation Program Required for Bone Marrow Exit and Control of Proliferation

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Interaction between ANXA1 and GATA-3 in Immunosuppression of CD4⁺ T Cells