Transcriptional repressor Blimp-1 regulates T cell homeostasis and function.
The B lymphocyte-induced maturation protein 1 (Blimp-1) transcriptional repressor is required for terminal differentiation of B lymphocytes. Here we document a function for Blimp-1 in the T cell lineage. Blimp-1-deficient thymocytes showed decreased survival and Blimp-1-deficient mice had more peripheral effector T cells. Mice lacking Blimp-1 developed severe colitis as early as 6 weeks of age, and Blimp-1-deficient regulatory T cells were defective in blocking the development of colitis. Blimp-1 mRNA expression increased substantially in response to T cell receptor stimulation. Compared with wild-type CD4(+) T cells, Blimp-1-deficient CD4(+) T cells proliferated more and produced excess interleukin 2 and interferon-gamma but reduced interleukin 10 after T cell receptor stimulation. These results emphasize a crucial function for Blimp-1 in controlling T cell homeostasis and activation.
Department of Microbiology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
Gislâine A
GA
Martins
Luisa
L
Cimmino
Miriam
M
Shapiro-Shelef
Matthias
M
Szabolcs
Alan
A
Herron
Erna
E
Magnusdottir
Kathryn
K
Calame
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D003092:Colitis / Q000209:etiology / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology; D006706:Homeostasis / Q000502:physiology; D051379:Mice; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D051560:Proto-Oncogene Proteins c-bcl-6; D012097:Repressor Proteins / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
C490010:Bcl6 protein, mouse; D016207:Cytokines; D004268:DNA-Binding Proteins; C513258:Prdm1 protein, mouse; D051560:Proto-Oncogene Proteins c-bcl-6; D012097:Repressor Proteins; D014157:Transcription Factors; D000074462:Positive Regulatory Domain I-Binding Factor 1