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Transcriptional repressor Blimp-1 regulates T cell homeostasis and function

Nature Immunology volume 7, pages 457–465 (2006)Cite this article

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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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.

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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.).

Author information

Author notes

  1. Gislâine A Martins, Luisa Cimmino and Miriam Shapiro-Shelef: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Microbiology, Columbia University College of Physicians and Surgeons, New York, 10032, New York, USA

    Gislâine A Martins, Miriam Shapiro-Shelef & Kathryn Calame

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

    Luisa Cimmino

  3. Department of Pathology, Columbia University College of Physicians and Surgeons, New York, 10032, New York, USA

    Matthias Szabolcs & Alan Herron

  4. Institute of Comparative Medicine, Columbia University College of Physicians and Surgeons, New York, 10032, New York, USA

    Alan Herron

  5. Department of Biological Sciences, Columbia University College of Physicians and Surgeons, New York, 10032, New York, USA

    Erna Magnusdottir

  6. Department of Biochemistry and Molecular Biophysics, Columbia University College of Physicians and Surgeons, New York, 10032, New York, USA

    Kathryn Calame

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Correspondence to Kathryn Calame.

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Supplementary information

Supplementary Table 1

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

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Martins, G., Cimmino, L., Shapiro-Shelef, M. et al. Transcriptional repressor Blimp-1 regulates T cell homeostasis and function. Nat Immunol 7, 457–465 (2006). https://doi.org/10.1038/ni1320

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