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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Dec 20, 2019 |
| Title |
microRNA-142–mediated repression of phosphodiesterase 3B critically regulates peripheral immune tolerance |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Tregs play a fundamental role in immune tolerance via control of self-reactive effector T cells (Teffs). This function is dependent on maintenance of a high intracellular cAMP concentration. A number of microRNAs are implicated in the maintenance of Tregs. In this study, we demonstrate that peripheral immune tolerance is critically dependent on posttranscriptional repression of the cAMP-hydrolyzing enzyme phosphodiesterase-3b (Pde3b) by microRNA-142-5p (miR-142-5p). In this manner, miR-142-5p acts as an immunometabolic regulator of intracellular cAMP, controlling Treg suppressive function. Mir142 was associated with a super enhancer bound by the Treg lineage–determining transcription factor forkhead box P3 (FOXP3), and Treg-specific deletion of miR-142 in mice (TregΔ142) resulted in spontaneous, lethal, multisystem autoimmunity, despite preserved numbers of phenotypically normal Tregs. Pharmacological inhibition and genetic ablation of PDE3B prevented autoimmune disease and reversed the impaired suppressive function of Tregs in TregΔ142 animals. These findings reveal a critical molecular switch, specifying Treg function through the modulation of a highly conserved, cell-intrinsic metabolic pathway. Modulation of this pathway has direct relevance to the pathogenesis and treatment of autoimmunity and cancer.
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| Overall design |
ChIP-seq to identify Foxp3 binding sites in murine Treg cells
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| Contributor(s) |
Anandagoda N, Willis JD, Hertweck A, Roberts LB, Jackson I, Gokmen M, Jenner RG, Howard JK, Lord GM |
| Citation(s) |
30741720 |
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| Submission date |
Aug 22, 2015 |
| Last update date |
Dec 22, 2019 |
| Contact name |
Richard Jenner |
| E-mail(s) |
r.jenner@ucl.ac.uk
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| Organization name |
UCL Cancer Institute
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| Department |
Cancer Biology
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| Lab |
Regulatory Genomics
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| Street address |
72 Huntley Street
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| City |
London |
| ZIP/Postal code |
WC1E 6BT |
| Country |
United Kingdom |
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| Platforms (2) |
| GPL11002 |
Illumina Genome Analyzer IIx (Mus musculus) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA293617 |
| SRA |
SRP062738 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE72279_RAW.tar |
110.0 Kb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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