Blimp-1 directly represses Il2 and the Il2 activator Fos, attenuating T cell proliferation and survival

GA Martins, L Cimmino, J Liao… - The Journal of …, 2008 - rupress.org
GA Martins, L Cimmino, J Liao, E Magnusdottir, K Calame
The Journal of experimental medicine, 2008rupress.org
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 …
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.
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