Your browser version may not work well with NCBI's Web applications. More information here...
Related Articles, Links
Click here to read Click here to read
Blimp-1 attenuates Th1 differentiation by repression of ifng, tbx21, and bcl6 gene expression.

Cimmino L, Martins GA, Liao J, Magnusdottir E, Grunig G, Perez RK, Calame KL.

The Institute of Human Nutrition, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.

T cell-specific deletion of Blimp-1 causes abnormal T cell homeostasis and function, leading to spontaneous, fatal colitis in mice. Herein we explore the role of Blimp-1 in Th1/Th2 differentiation. Blimp-1 mRNA and protein are more highly expressed in Th2 cells compared with Th1 cells, and Blimp-1 attenuates IFN-gamma production in CD4 cells activated under nonpolarizing conditions. Although Blimp-1-deficient T cells differentiate normally to Th2 cytokines in vitro, Blimp-1 is required in vivo for normal Th2 humoral responses to NP-KLH (4-hydroxy-3-nitrophenylacetyl/keyhole lymphocyte hemocyanin) immunization. Lack of Blimp-1 in CD4 T cells causes increased IFN-gamma, T-bet, and Bcl-6 mRNA. By chromatin immunoprecipitation we show that Blimp-1 binds directly to a distal regulatory region in the ifng gene and at multiple sites in tbx21 and bcl6 genes. Our data provide evidence that Blimp-1 functions in Th2 cells to reinforce Th2 differentiation by repressing critical Th1 genes.

PMID: 18684923 [PubMed - indexed for MEDLINE]