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 �...

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Bibliographic Details
Published in:Nature Immunology 2006-05, Vol.7 (5), p.466-474
Main Authors: Nutt, Stephen L, Kallies, Axel, Hawkins, Edwin D, Belz, Gabrielle T, Metcalf, Donald, Hommel, Mirja, Corcoran, Lynn M, Hodgkin, Philip D
Format: Article
Language:English
Subjects:
Accumulation
Animals
Apoptosis
Autoimmune diseases
B-Lymphocytes - immunology
Biomedical and Life Sciences
Biomedicine
Cell Differentiation
Deoxyribonucleic acid
DNA
Down-Regulation - immunology
Genetic aspects
Health aspects
Homeostasis
Homeostasis - immunology
Immune system
Immunologic Memory - drug effects
Immunology
Infectious Diseases
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Pathology
Physiological aspects
Positive Regulatory Domain I-Binding Factor 1
Prevention
Repressor Proteins - genetics
Repressor Proteins - metabolism
Repressor Proteins - pharmacology
Self Tolerance - immunology
Stem cells
T cells
T-Lymphocytes - cytology
T-Lymphocytes - immunology
Transcription Factors - genetics
Transcription Factors - metabolism
Transcription Factors - pharmacology
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Summary: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.
ISSN:1529-2908
1529-2916
1365-2567
DOI:10.1038/ni1321