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Control of the inheritance of regulatory T cell identity by a cis element in the Foxp3 locus
Control of the inheritance of regulatory T cell identity by a cis element in the Foxp3 locus
- Publication Year :
- 2014
-
Abstract
- SummaryIn multicellular organisms, specialized functions are delegated to distinct cell types whose identity and functional integrity are maintained upon challenge. However, little is known about the mechanisms enabling lineage inheritance and their biological implications. Regulatory T (Treg) cells, which express the transcription factor Foxp3, suppress fatal autoimmunity throughout the lifespan of animals. Here, we show that a dedicated Foxp3 intronic element CNS2 maintains Treg cell lineage identity by acting as a sensor of the essential Treg cell growth factor IL-2 and its downstream target STAT5. CNS2 sustains Foxp3 expression during division of mature Treg cells when IL-2 is limiting and counteracts proinflammatory cytokine signaling that leads to the loss of Foxp3. CNS2-mediated stable inheritance of Foxp3 expression is critical for adequate suppression of diverse types of chronic inflammation by Treg cells and prevents their differentiation into inflammatory effector cells. The described mechanism may represent a general principle of the inheritance of differentiated cell states.
- Subjects :
- Interleukin 2
Cell type
Regulatory T cell
Cellular differentiation
chemical and pharmacologic phenomena
Biology
T-Lymphocytes, Regulatory
General Biochemistry, Genetics and Molecular Biology
Article
Mice
medicine
STAT5 Transcription Factor
Animals
Regulatory Elements, Transcriptional
Transcription factor
Genetics
Inflammation
Effector
Biochemistry, Genetics and Molecular Biology(all)
FOXP3
hemic and immune systems
Forkhead Transcription Factors
DNA Methylation
Introns
medicine.anatomical_structure
Interleukin-2
CpG Islands
Signal transduction
medicine.drug
Signal Transduction
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....8bee1b06c6fbf61325d6a567dc6f7e31