Control of the inheritance of regulatory T cell identity by a cis element in the Foxp3 locus Journal Article
| Authors: | Feng, Y.; Arvey, A.; Chinen, T.; Van Der Veeken, J.; Gasteiger, G.; Rudensky, A. Y. |
| Article Title: | Control of the inheritance of regulatory T cell identity by a cis element in the Foxp3 locus |
| Abstract: | In 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. |
| Keywords: | protein expression; nonhuman; transcription factor foxp3; animal cell; mouse; cell cycle; cell division; interleukin 2; cell growth; cell maturation; animal experiment; cell differentiation; cell lineage; regulatory t lymphocyte; nucleotide sequence; effector cell; chronic inflammation; downstream processing; intracellular signaling; inheritance; article |
| Journal Title: | Cell |
| Volume: | 158 |
| Issue: | 4 |
| ISSN: | 0092-8674 |
| Publisher: | Cell Press |
| Date Published: | 2014-08-14 |
| Start Page: | 749 |
| End Page: | 763 |
| Language: | English |
| DOI: | 10.1016/j.cell.2014.07.031 |
| PROVIDER: | scopus |
| PMCID: | PMC4151558 |
| PUBMED: | 25126783 |
| DOI/URL: | |
| Notes: | Export Date: 1 December 2014 -- Source: Scopus |
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