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| Status |
Public on Dec 23, 2013 |
| Title |
Involvement of Nr4a in a Treg-specific transcriptional program and suppression of　Th2/Tfh response |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
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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| Overall design |
mRNA from wild-type and Nr4a-deficient Treg cells were analyzed.
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| Contributor(s) |
Sekiya T, Yoshimura A |
| Citation missing |
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| Submission date |
Dec 22, 2013 |
| Last update date |
Feb 02, 2018 |
| Contact name |
Takashi Sekiya |
| E-mail(s) |
lb-sekiya@hospk.ncgm.go.jp
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| Organization name |
National Center for Global Health and Medicine
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| Street address |
1-7-1 Kohnodai
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| City |
Ichikawa |
| State/province |
Chiba |
| ZIP/Postal code |
272-0827 |
| Country |
Japan |
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| Platforms (1) |
| GPL10787 |
Agilent-028005 SurePrint G3 Mouse GE 8x60K Microarray (Probe Name version) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA232428 |
