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

Catherine Konopacki, Yuri Pritykin, Yury Rubtsov, Christina S. Leslie, Alexander Y. Rudensky

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Regulatory T cells (T reg cells), whose differentiation and function are controlled by transcription factor Foxp3, express the closely related family member Foxp1. Here we explored Foxp1 function in T reg cells. We found that a large number of Foxp3-bound genomic sites in T reg cells were occupied by Foxp1 in both T reg cells and conventional T cells (T conv cells). In T reg cells, Foxp1 markedly increased Foxp3 binding to these sites. Foxp1 deficiency in T reg 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 T reg cells were fully or partially rescued by strong IL-2 signaling. Our studies suggest that Foxp1 serves an essential non-redundant function in T reg cells by enforcing Foxp3-mediated regulation of gene expression and enabling efficient IL-2 signaling in these cells.

Original languageEnglish (US)
Pages (from-to)232-242
Number of pages11
JournalNature Immunology
Volume20
Issue number2
DOIs
StatePublished - Feb 1 2019
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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