Transcription factor Foxp1 regulates Foxp3 chromatin binding and coordinates regulatory T cell function Journal Article

   

Authors:	Konopacki, C.; Pritykin, Y.; Rubtsov, Y.; Leslie, C. S.; Rudensky, A. Y.
Article Title:	Transcription factor Foxp1 regulates Foxp3 chromatin binding and coordinates regulatory T cell function
Abstract:	Regulatory T cells (Treg cells), whose differentiation and function are controlled by transcription factor Foxp3, express the closely related family member Foxp1. Here we explored Foxp1 function in Treg cells. We found that a large number of Foxp3-bound genomic sites in Treg cells were occupied by Foxp1 in both Treg cells and conventional T cells (Tconv cells). In Treg cells, Foxp1 markedly increased Foxp3 binding to these sites. Foxp1 deficiency in Treg cells resulted in their impaired function and competitive fitness, associated with markedly reduced CD25 expression and interleukin-2 (IL-2) responsiveness, diminished CTLA-4 expression and increased SATB1 expression. The characteristic expression patterns of CD25, Foxp3 and CTLA-4 in Treg cells were fully or partially rescued by strong IL-2 signaling. Our studies suggest that Foxp1 serves an essential non-redundant function in Treg cells by enforcing Foxp3-mediated regulation of gene expression and enabling efficient IL-2 signaling in these cells. © 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.
Journal Title:	Nature Immunology
Volume:	20
Issue:	2
ISSN:	1529-2908
Publisher:	Nature Publishing Group
Date Published:	2019-02-01
Start Page:	232
End Page:	242
Language:	English
DOI:	10.1038/s41590-018-0291-z
PUBMED:	30643266
PROVIDER:	scopus
PMCID:	PMC7534899
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85059939011&doi=10.1038%2fs41590-018-0291-z&partnerID=40&md5=c093be5daba531c3272c878526ecf050
Notes:	Export Date: 1 February 2019 -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/139561