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Publication : Transcription factor Foxp1 regulates Foxp3 chromatin binding and coordinates regulatory T cell function.

First Author  Konopacki C Year  2019
Journal  Nat Immunol Volume  20
Issue  2 Pages  232-242
PubMed ID  30643266 Mgi Jnum  J:282453
Mgi Id  MGI:6380975 Doi  10.1038/s41590-018-0291-z
Citation  Konopacki C, et al. (2019) Transcription factor Foxp1 regulates Foxp3 chromatin binding and coordinates regulatory T cell function. Nat Immunol 20(2):232-242
abstractText  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.
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