Blimp-1 attenuates Th1 differentiation by repression of ifng, tbx21, and bcl6 gene expression.
J Immunol
; 181(4): 2338-47, 2008 Aug 15.
Article
em En
| MEDLINE
| ID: mdl-18684923
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
/
Fatores de Transcrição
/
Diferenciação Celular
/
Interferon gama
/
Células Th1
/
Proteínas com Domínio T
/
Proteínas de Ligação a DNA
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Estados Unidos