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Transcriptional repressor Blimp-1 regulates T cell homeostasis and function

Abstract

The B lymphocyte–induced maturation protein 1 (Blimp-1) transcriptional repressor is required for terminal differentiation of B lymphocytes. Here we document a function for Blimp-1 in the T cell lineage. Blimp-1-deficient thymocytes showed decreased survival and Blimp-1-deficient mice had more peripheral effector T cells. Mice lacking Blimp-1 developed severe colitis as early as 6 weeks of age, and Blimp-1-deficient regulatory T cells were defective in blocking the development of colitis. Blimp-1 mRNA expression increased substantially in response to T cell receptor stimulation. Compared with wild-type CD4+ T cells, Blimp-1-deficient CD4+ T cells proliferated more and produced excess interleukin 2 and interferon-γ but reduced interleukin 10 after T cell receptor stimulation. These results emphasize a crucial function for Blimp-1 in controlling T cell homeostasis and activation.

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Acknowledgements

We thank H. Gu and Y.-R. Zou for advice and for critical reading of the manuscript; the Calame laboratory for advice; J. Liao for assistance with the mice; and D. Savitsky for help with the DSS colitis experiments. Supported by the National Institutes of Health (RO1 AI50659 and RO1 AI43576 to K.C.).

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Competing interests

The authors declare no competing financial interests.

Correspondence to Kathryn Calame.

Supplementary information

  1. Supplementary Table 1

    Primer sequences used for Quantitative PCR. (PDF 10 kb)

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Figure 1: The generation and phenotype of CKO mice.
Figure 2: Blimp-1 transcripts in T lineage cells.
Figure 3: Thymocyte development in CKO mice.
Figure 4: Hyperactivation of CKO peripheral T cells.
Figure 5: Treg cells in CKO mice.
Figure 6: Blimp-1 in colitis.
Figure 7: Hyper-responsive CKO CD4+ T cells.
Figure 8: IFN-γ, IL-4 and IL-10-production in CD4+ CKO T cells.