Roles of Nr4a family transcription factors in Th and Treg cell differentiation from Tnaive cells
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PROVIDER: PRJNA644550 | ENA |
REPOSITORIES: ENA
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Project description:Regulatory T (Treg) cells, as central mediators of immune suppression, play crucial roles in many aspects of immune system physiology and pathophysiology. Treg cells are characterized by a distinct pattern of gene expression, including upregulation of immune-suppressive genes and silencing of inflammatory cytokine genes. However, the molecular mechanisms that establish and/or maintain such gene regulation in Treg cells remain largely unknown. We recently reported that Nr4a family nuclear orphan receptors are essential for the development of Treg cells. The fact that Treg cells maintain high levels of expression of all Nr4a family components suggests that they may also play critical roles beyond Treg cell development. Thus, we compared mRNA expression pattern between wild-type Treg cells and Nr4a-deficietn Treg cells. As a result, we found that expression of 'Treg-signature genes' were globally down regulated in Nr4a-deficient Treg cells. mRNA from wild-type and Nr4a-deficient Treg cells were analyzed.
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Project description:In this study, we investigated the roles of Nr4a family transcription factors in Th and Treg cell differentiation from Tnaive cells. Nr4a factors were found to promote Treg cell differentiation and repress Th1 and Th2 differentiation. During Treg cell differentiation, all Nr4a factors are transiently induced in Tnaive cells immediately after TCR stimulation, whereby they mediate epigenetic changes directly or by cooperating with other transcription factors. To reveal Nr4a factors' mediated transcrptional events, we analyzed gene expression of wild type and Nr4a-tripple knockout (Nr4a-TKO) Tnaive and iTreg cells by microarray analysis.
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Project description:Regulatory T (Treg) cells, as central mediators of immune suppression, play crucial roles in many aspects of immune system physiology and pathophysiology. Treg cells are characterized by a distinct pattern of gene expression, including upregulation of immune-suppressive genes and silencing of inflammatory cytokine genes. However, the molecular mechanisms that establish and/or maintain such gene regulation in Treg cells remain largely unknown. We recently reported that Nr4a family nuclear orphan receptors are essential for the development of Treg cells. The fact that Treg cells maintain high levels of expression of all Nr4a family components suggests that they may also play critical roles beyond Treg cell development. Here, we show that Nr4a factors are essential for maintaining Treg-specific gene expression programs, mediating two defined characteristics of Treg cells: lineage stability and suppressive activity. A compound knockout mouse strain in which all Nr4a genes were specifically deleted in Treg cells developed systemic immunopathology with accelerated Th2/Tfh/IgE reactions. Treg cells in these mice showed global reduction of 'Treg signature' gene expression, including Foxp3, Il2ra and Ikzf4. These findings demonstrate that Nr4a controls a genetic program indispensable for Treg cell maintenance and function. mRNA from wild-type and Nr4a-deficient Treg cells were analyzed.
2013-12-23 | E-GEOD-53574 | biostudies-arrayexpress
Project description:In this study, we investigated the roles of Nr4a family transcription factors in Th and Treg cell differentiation from Tnaive cells. Nr4a factors were found to promote Treg cell differentiation and repress Th1 and Th2 differentiation. During Treg cell differentiation, all Nr4a factors are transiently induced in Tnaive cells immediately after TCR stimulation, whereby they mediate epigenetic changes directly or by cooperating with other transcription factors. To reveal Nr4a factors' mediated transcrptional events, we analyzed gene expression of wild type and Nr4a1,a2,a3-tripple knockout (Nr4a-TKO) iTreg cells by microarray analysis.
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Project description:Regulatory T (Treg) cells, as central mediators of immune suppression, play crucial roles in many aspects of immune system physiology and pathophysiology. Treg cells are characterized by a distinct pattern of gene expression, including upregulation of immune-suppressive genes and silencing of inflammatory cytokine genes. However, the molecular mechanisms that establish and/or maintain such gene regulation in Treg cells remain largely unknown. We recently reported that Nr4a family nuclear orphan receptors are essential for the development of Treg cells. The fact that Treg cells maintain high levels of expression of all Nr4a family components suggests that they may also play critical roles beyond Treg cell development. Thus, we compared mRNA expression pattern between wild-type Treg cells and Nr4a-deficietn Treg cells. As a result, we found that expression of 'Treg-signature genes' were globally down regulated in Nr4a-deficient Treg cells.
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Project description:Regulatory T (Treg) cells, as central mediators of immune suppression, play crucial roles in many aspects of immune system physiology and pathophysiology. Treg cells are characterized by a distinct pattern of gene expression, including upregulation of immune-suppressive genes and silencing of inflammatory cytokine genes. However, the molecular mechanisms that establish and/or maintain such gene regulation in Treg cells remain largely unknown. We recently reported that Nr4a family nuclear orphan receptors are essential for the development of Treg cells. The fact that Treg cells maintain high levels of expression of all Nr4a family components suggests that they may also play critical roles beyond Treg cell development. Here, we show that Nr4a factors are essential for maintaining Treg-specific gene expression programs, mediating two defined characteristics of Treg cells: lineage stability and suppressive activity. A compound knockout mouse strain in which all Nr4a genes were specifically deleted in Treg cells developed systemic immunopathology with accelerated Th2/Tfh/IgE reactions. Treg cells in these mice showed global reduction of 'Treg signature' gene expression, including Foxp3, Il2ra and Ikzf4. These findings demonstrate that Nr4a controls a genetic program indispensable for Treg cell maintenance and function.
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