Foxp1 is an essential transcriptional regulator for the generation of quiescent naive T cells during thymocyte development.
Proper thymocyte development is required to establish T-cell central tolerance and to generate naive T cells, both of which are essential for T-cell homeostasis and a functional immune system. Here we demonstrate that the loss of transcription factor Foxp1 results in the abnormal development of T cells. Instead of generating naive T cells, Foxp1-deficient single-positive thymocytes acquire an activated phenotype prematurely in the thymus and lead to the generation of peripheral CD4(+) T and CD8(+) T cells that exhibit an activated phenotype and increased apoptosis and readily produce cytokines upon T-cell receptor engagement. These results identify Foxp1 as an essential transcriptional regulator for thymocyte development and the generation of quiescent naive T cells.
Feng
Xiaoming
X
Immunology Program and Wistar Vaccine Center, The Wistar Institute, Philadelphia, PA, USA.
Ippolito
Gregory C
GC
Tian
Lifeng
L
Wiehagen
Karla
K
Oh
Soyoung
S
Sambandam
Arivazhagan
A
Willen
Jessica
J
Bunte
Ralph M
RM
Maika
Shanna D
SD
Harriss
June V
JV
Caton
Andrew J
AJ
Bhandoola
Avinash
A
Tucker
Philip W
PW
Hu
Hui
H
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics* / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000502:physiology*; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D013601:T-Lymphocytes / Q000378:metabolism / Q000502:physiology*; D013950:Thymus Gland / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology
D051858:Forkhead Transcription Factors; C432917:Foxp1 protein, mouse; D012097:Repressor Proteins; D014157:Transcription Factors