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Status |
Public on May 10, 2021 |
Title |
Foxp3 enhancers synergize to maximize regulatory T cell suppressive capacity [Capture-C] |
Organism |
Mus musculus |
Experiment type |
Other
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Summary |
Treg cells bearing a diverse antigen receptor repertoire suppress pathogenic T cells and maintain immune homeostasis during their long lifespan. How their robust function is determined genetically remains elusive. Here, we investigate the regulatory space of the cis-regulatory elements of Treg lineage–specifying factor Foxp3. Foxp3 enhancers are known as distinct readers for environmental cues in promoting Treg cell induction or lineage stability. However, their single deficiencies cause mild, if any, immune dysregulation, leaving the key transcriptional mechanisms determining Foxp3 expression and thereby Treg suppressive capacity uncertain. We examined the collective activities of Foxp3 enhancers and found that they coordinate to maximize Treg cell induction, Foxp3 expression level, or lineage stability through distinct modes and that ablation of synergistic enhancers led to lethal autoimmunity in young mice. Thus, the induction and maintenance of a diverse, stable Treg cell repertoire rely on combinatorial Foxp3 enhancers, suggesting broad, stage-specific, synergistic activities of cell-intrinsic factors and -extrinsic cues in determining Treg suppressive capacity.
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Overall design |
Capture-C was used to assess the three-dimensional chromatin architecture around the Foxp3 locus in Treg precursor cells (i.e., CD4 naïve T cells), ASC-treated iTreg cells, and natural Treg cells.
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Contributor(s) |
Wright S, Li C, Xu B, Li J, Zong X, Feng Y |
Citation(s) |
34086055 |
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Submission date |
Mar 22, 2021 |
Last update date |
Aug 09, 2021 |
Contact name |
Beisi Xu |
E-mail(s) |
beisi.xu@stjude.org
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Organization name |
St Jude Children's Research Hosipital
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Department |
Center for Applied Bioinformatics
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Street address |
262 Danny Thomas Pl
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City |
Memphis |
State/province |
Tennessee |
ZIP/Postal code |
38105 |
Country |
USA |
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Platforms (1) |
GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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Samples (10)
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GSM5201391 |
Capture C_Tn-1 (CD4+GFP+CD62L+CD44- naive T cells sorted from male Foxp3-GFP mice) |
GSM5201392 |
Capture C_Tn-2 (CD4+GFP+CD62L+CD44- naive T cells sorted from male Foxp3-GFP mice) |
GSM5201393 |
Capture C_Tn-3 (CD4+GFP+CD62L+CD44- naive T cells sorted from male Foxp3-GFP mice) |
GSM5201394 |
Capture C_ASC-treated iTreg-1 (CD4+GFP+ iTreg cells induced from naive T cells of male Foxp3-GFP mice) |
GSM5201395 |
Capture C_ASC-treated iTreg-2 (CD4+GFP+ iTreg cells induced from naive T cells of male Foxp3-GFP mice) |
GSM5201396 |
Capture C_ASC-treated iTreg-3 (CD4+GFP+ iTreg cells induced from naive T cells of male Foxp3-GFP mice) |
GSM5201397 |
Capture C_nTreg-1(CD4+YFP+ Treg cells sorted from male Foxp3-YFP-Cre mice) |
GSM5201398 |
Capture C_nTreg-2(CD4+GFP+ Treg cells sorted from male Foxp3-DTR-GFP mice) |
GSM5201399 |
Capture C_Tn-1 (CD4+CD25-CD62L+CD44- Tn cells sorted from male B6 mice) |
GSM5201400 |
Capture C_Tn-2 (CD4+CD25-CD62L+CD44- Tn cells sorted from male B6 mice) |
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This SubSeries is part of SuperSeries: |
GSE158223 |
Foxp3 enhancers synergize to maximize regulatory T cell suppressive capacity |
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Relations |
BioProject |
PRJNA716354 |
SRA |
SRP311708 |