Transcriptional repressor Blimp-1 is essential for T cell homeostasis and self-tolerance.
T cell homeostasis is crucial for a functional immune system, as the accumulation of T cells resulting from lack of regulatory T cells or an inability to shut down immune responses can lead to inflammation and autoimmune pathology. Here we show that Blimp-1, a transcriptional repressor that is a 'master regulator' of terminal B cell differentiation, was expressed in a subset of antigen-experienced CD4(+) and CD8(+) T cells. Mice reconstituted with fetal liver stem cells expressing a mutant Blimp-1 lacking the DNA-binding domain developed a lethal multiorgan inflammatory disease caused by an accumulation of effector and memory T cells. These data identify Blimp-1 as an essential regulator of T cell homeostasis and suggest that Blimp-1 regulates both B cell and T cell differentiation.
Kallies
Axel
A
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia.
Hawkins
Edwin D
ED
Belz
Gabrielle T
GT
Metcalf
Donald
D
Hommel
Mirja
M
Corcoran
Lynn M
LM
Hodgkin
Philip D
PD
Nutt
Stephen L
SL
D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D015536:Down-Regulation / Q000276:immunology*; D006706:Homeostasis / Q000276:immunology*; D007156:Immunologic Memory / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D000074462:Positive Regulatory Domain I-Binding Factor 1; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D017634:Self Tolerance / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
C513258:Prdm1 protein, mouse; D012097:Repressor Proteins; D014157:Transcription Factors; D000074462:Positive Regulatory Domain I-Binding Factor 1