The transcription factor Foxp1 preserves integrity of an active Foxp3 locus in extrathymic Treg cells
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SCOPUS
- Title
- The transcription factor Foxp1 preserves integrity of an active Foxp3 locus in extrathymic Treg cells
- Authors
- Sayantani Ghosh; Roy-Chowdhuri, Sinchita; Kang, Keunsoo; IM, SIN HYEOG; Rudra, Dipayan
- Date Issued
- 2018-10
- Publisher
- NATURE PUBLISHING GROUP
- Abstract
- Regulatory T (Treg) cells, which are broadly classified as thymically derived (tTreg) or extrathymically induced (iTreg), suppress immune responses and display stringent dependence to the transcription factor Foxp3. However precise understanding of molecular events that promote and preserve Foxp3 expression in Treg cells is still evolving. Here we show that Foxpl, a forkhead transcription factor and a sibling family member of Foxp3, is essential for sustaining optimal expression of Foxp3 specifically in iTreg cells. Deletion of Foxp1 renders iTreg cells to gradually lose Foxp3, resulting in dramatically reduced Nrp1(-)Helios(-) iTreg compartment as well as augmented intestinal inflammation in aged mice. Our finding underscores a mechanistic module in which evolutionarily related transcription factors establish a molecular program to ensure efficient immune homeostasis. Furthermore, it provides a novel target that can be potentially modulated to exclusively reinforce iTreg stability keeping their thymic counterpart unperturbed.
- Keywords
- forkhead transcription factor; transcription factor foxp1; transcription factor FOXP3; unclassified drug; DNA binding protein; forkhead transcription factor; Foxp1 protein, mouse; Foxp3 protein, mouse; histone; neuropilin 1; repressor protein; transcription factor; Zfpn1a2 protein, mouse; cell; gene; gene expression; homeostasis; immune response; rodent; aged; Article; controlled study; gene deletion; gene locus; homeostasis; immunological tolerance; immunomodulation; mouse; nonhuman; protein expression; regulatory T lymphocyte; animal; C57BL mouse; cell differentiation; colitis; gene expression; genetics; immunology; inflammation; intestine mucosa; metabolism; pathology; physiology; regulatory sequence; regulatory T lymphocyte; Mus; Animals; Cell Differentiation; Colitis; DNA-Binding Proteins; Forkhead Transcription Factors; Gene Deletion; Gene Expression; Histones; Inflammation; Intestinal Mucosa; Mice; Mice, Inbred C57BL; Neuropilin-1; Regulatory Sequences, Nucleic Acid; Repressor Proteins; T-Lymphocytes, Regulatory; Transcription Factors
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/94275
- DOI
- 10.1038/s41467-018-07018-y
- ISSN
- 2041-1723
- Article Type
- Article
- Citation
- NATURE COMMUNICATIONS, vol. 9, no. 1, 2018-10
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