Blimp-1 Attenuates Th1 Differentiation by Repression of ifng, tbx21, and bcl6 Gene Expression

• Published in: The Journal of immunology (1950) Vol. 181; no. 4; pp. 2338 - 2347
• Main Authors: Cimmino, Luisa, Martins, Gislaine A, Liao, Jerry, Magnusdottir, Erna, Grunig, Gabriele, Perez, Rocio K, Calame, Kathryn L
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.08.2008
• Subjects: Animals; Cell Differentiation - genetics; Cell Differentiation - immunology; Cells, Cultured; DNA-Binding Proteins - antagonists & inhibitors; DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - deficiency; DNA-Binding Proteins - physiology; Gene Expression Regulation - immunology; Growth Inhibitors - biosynthesis; Growth Inhibitors - deficiency; Growth Inhibitors - physiology; Interferon-gamma - antagonists & inhibitors; Interferon-gamma - biosynthesis; Interferon-gamma - genetics; Lymphocyte Depletion; Mice; Mice, Knockout; Mice, Transgenic; Positive Regulatory Domain I-Binding Factor 1; Proto-Oncogene Proteins c-bcl-6; Repressor Proteins - biosynthesis; Repressor Proteins - genetics; Repressor Proteins - physiology; T-Box Domain Proteins - antagonists & inhibitors; T-Box Domain Proteins - biosynthesis; T-Box Domain Proteins - genetics; Th1 Cells - cytology; Th1 Cells - immunology; Th1 Cells - metabolism; Th2 Cells - cytology; Th2 Cells - immunology; Th2 Cells - metabolism; Transcription Factors - biosynthesis; Transcription Factors - deficiency; Transcription Factors - genetics; Transcription Factors - physiology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.181.4.2338

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.