Blimp-1 directly represses Il2 and the Il2 activator Fos, attenuating T cell proliferation and survival.
Mice with a T cell-specific deletion of Prdm1, encoding Blimp-1, have aberrant T cell homeostasis and develop fatal colitis. In this study, we show that one critical activity of Blimp-1 in T cells is to repress IL-2, and that it does so by direct repression of Il2 transcription, and also by repression of Fos transcription. Using these mechanisms Blimp-1 participates in an autoregulatory loop by which IL-2 induces Prdm1 expression and thus represses its own expression after T cell activation, ensuring that the immune response is appropriately controlled. This activity of Blimp-1 is important for cytokine deprivation-induced T cell death and for attenuating T cell proliferation in antigen-specific responses both in vitro and in vivo.
Martins
Gislâine A
GA
Department of Microbiology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA. martinsg@cshs.org
Cimmino
Luisa
L
Liao
Jerry
J
Magnusdottir
Erna
E
Calame
Kathryn
K
D000818:Animals; D017951:Antigen Presentation; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D006706:Homeostasis; D007107:Immune System; D007376:Interleukin-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D000074462:Positive Regulatory Domain I-Binding Factor 1; D017434:Protein Structure, Tertiary; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology*; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic
D007376:Interleukin-2; C513258:Prdm1 protein, mouse; D016760:Proto-Oncogene Proteins c-fos; D014157:Transcription Factors; D000074462:Positive Regulatory Domain I-Binding Factor 1