Blimp‐1 directly represses il2 and the gene encoding il2 transcriptional activator Fos

The transcriptional repressor B‐lymphocyte‐induced maturation protein 1 (Blimp‐1) was initially studied for its crucial role in plasmacytic differentiation. More recent studies, however, have demonstrated that Blimp‐1 is expressed in T lymphocytes and plays important roles for the function of these cells. T‐cell specific deletion of Blimp‐1 (CKO mice) disrupts the homeostasis of CD4 + and CD8 + T cells, resulting in accumulation of antigen‐experienced cells in the periphery and culminating in the spontaneous development of colitis. We have previously reported that lack of Blimp‐1 in T cells results in increased production of IL‐2. We now present evidence that Blimp‐1 represses transcription of the il2 gene in CD4+ T cells by acting in at least two different ways: Blimp‐1 directly represses il2 and the gene encoding il2 ‐activator Fos, as demonstrated by chromatin immunoprecipitation (ChIP) assays in primary CD4+ T cells. Accordingly, IL‐2 and Fos steady‐state mRNA levels are elevated in Blimp‐1 deficient CD4+ T cells compared to Blimp‐1 sufficient cells. The implications of this regulation of IL‐2 by Blimp‐1 in vivo are currently been investigated and preliminary evidence suggests that Blimp‐1 is a critical component of a recently reported IL‐2 auto‐regulatory circuit that controls the development of effector responses.