Article | Published:

Vitamin D controls T cell antigen receptor signaling and activation of human T cells

Nature Immunology volume 11, pages 344349 (2010) | Download Citation

Abstract

Phospholipase C (PLC) isozymes are key signaling proteins downstream of many extracellular stimuli. Here we show that naive human T cells had very low expression of PLC-γ1 and that this correlated with low T cell antigen receptor (TCR) responsiveness in naive T cells. However, TCR triggering led to an upregulation of 75-fold in PLC-γ1 expression, which correlated with greater TCR responsiveness. Induction of PLC-γ1 was dependent on vitamin D and expression of the vitamin D receptor (VDR). Naive T cells did not express VDR, but VDR expression was induced by TCR signaling via the alternative mitogen-activated protein kinase p38 pathway. Thus, initial TCR signaling via p38 leads to successive induction of VDR and PLC-γ1, which are required for subsequent classical TCR signaling and T cell activation.

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Acknowledgements

We thank Bayer Schering Pharma AG for the VDR antagonists ZK191784 and ZK203278. Supported by The Danish Medical Research Council, The Lundbeck Foundation, The Novo Nordisk Foundation, The King Christian the 10th Foundation and The A.P. Møller Foundation for the Advancement of Medical Sciences.

Author information

Affiliations

  1. Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.

    • Marina Rode von Essen
    • , Martin Kongsbak
    • , Niels Ødum
    •  & Carsten Geisler
  2. Center for Healthy Aging, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.

    • Peter Schjerling
  3. Department of Biology, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.

    • Niels Ødum
  4. Institute of Sports Medicine, Bispebjerg Hospital, Rigshospitalet and Faculty of Health Sciences, University of Copenhagen, Denmark.

    • Peter Schjerling
  5. Department of Nephrology, Rigshospitalet and Faculty of Health Sciences, University of Copenhagen, Denmark.

    • Klaus Olgaard

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Contributions

M.R.v.E. did most of the experiments, analyzed data and contributed to the writing of the manuscript; M.K. and P.S. contributed to the ketoconazole and mRNA experiments; K.O. contributed to the planning and analyses of studies involving patients; N.Ø. contributed to the design and analysis of some of the experiments; and C.G. conceptualized the research, directed the study, analyzed data and wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Carsten Geisler.

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DOI

https://doi.org/10.1038/ni.1851

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