TY - JOUR
T1 - Transcription factor Foxp1 regulates Foxp3 chromatin binding and coordinates regulatory T cell function
AU - Konopacki, Catherine
AU - Pritykin, Yuri
AU - Rubtsov, Yury
AU - Leslie, Christina S.
AU - Rudensky, Alexander Y.
N1 - Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2019/2/1
Y1 - 2019/2/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85059939011&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85059939011&partnerID=8YFLogxK
U2 - 10.1038/s41590-018-0291-z
DO - 10.1038/s41590-018-0291-z
M3 - Article
C2 - 30643266
AN - SCOPUS:85059939011
SN - 1529-2908
VL - 20
SP - 232
EP - 242
JO - Nature Immunology
JF - Nature Immunology
IS - 2
ER -