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| Status |
Public on Dec 18, 2018 |
| Title |
c-Maf-dependent Treg cell control of intestinal TH17 cells and IgA establishes host–microbiota homeostasis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Foxp3+ regulatory T (Treg) cells are essential for immunological tolerance and homeostasis. In peripheral tissues, Treg cells acquire enhanced suppressive functions and co-opt distinct transcriptional modules, allowing context and tissue-dependent immune regulation. Here we show that the transcription factor c-Maf was highly expressed by effector Treg cells and controlled their IL-10 production. In the intestine, c-Maf was required for the differentiation of RORgt+ microbiota-dependent Treg cells, and restricted their production of inflammatory cytokines. Consequently, Treg cell-specific loss of c-Maf resulted in perturbed intestinal homeostasis, microbial dysbiosis and a selective failure to control Th17 responses during homeostasis and upon chemically induced epithelial damage. Molecular profiling revealed that c-Maf regulated expression of key genes of the transcriptional signature of intestinal Treg cells, including Rorc and Il10. Thus, our study identifies a key role of c-Maf in preserving the identity and function of intestinal Treg cells, essential for the control of intestinal immune homeostasis.
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| |
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| Overall design |
Transcriptional profiling of control (Foxp3Cre-YFP, "WT") and Maf-KO (Maffl/fl x Foxp3Cre-YFP, "KO") Treg cells sorted from Gut and Spleen
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| |
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| Contributor(s) |
Liao Y, Hu Y, Shi W, Neumann C, Mashreghi M, Scheffold A, Kallies A |
| Citation(s) |
30778241 |
| |
| Submission date |
Nov 01, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Wei Shi |
| E-mail(s) |
Wei.Shi@onjcri.org.au
|
| Organization name |
Olivia Newton John Cancer Research Institute
|
| Department |
Bioinformatics and Cancer Genomics
|
| Street address |
Level 5, ONJ Cancer Centre, 145 Studley Rd
|
| City |
Heidelberg |
| State/province |
VIC |
| ZIP/Postal code |
3084 |
| Country |
Australia |
| |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (10)
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| Relations |
| BioProject |
PRJNA416713 |
| SRA |
SRP123325 |
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