Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Brief Communication
  • Published:

Human TH17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation

Abstract

TH17 lymphocytes appear to be essential in the pathogenesis of numerous inflammatory diseases. We demonstrate here the expression of IL-17 and IL-22 receptors on blood-brain barrier endothelial cells (BBB-ECs) in multiple sclerosis lesions, and show that IL-17 and IL-22 disrupt BBB tight junctions in vitro and in vivo. Furthermore, TH17 lymphocytes transmigrate efficiently across BBB-ECs, highly express granzyme B, kill human neurons and promote central nervous system inflammation through CD4+ lymphocyte recruitment.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: TH17 lymphocytes migrate efficiently across the BBB in vitro and in vivo and kill human neurons.
Figure 2: IL-17 and IL-22 receptors are expressed on human brain endothelium, and their activation permeabilizes the BBB.

Similar content being viewed by others

References

  1. Renno, T. et al. Int. Immunol. 6, 347–354 (1994).

    Article  CAS  Google Scholar 

  2. Bettelli, E. et al. J. Exp. Med. 200, 79–87 (2004).

    Article  CAS  Google Scholar 

  3. Steinman, L. Nat. Med. 13, 139–145 (2007).

    Article  CAS  Google Scholar 

  4. Cua, D.J. et al. Nature 421, 744–748 (2003).

    Article  CAS  Google Scholar 

  5. Langrish, C.L. et al. J. Exp. Med. 201, 233–240 (2005).

    Article  CAS  Google Scholar 

  6. Sospedra, M. & Martin, R. Annu. Rev. Immunol. 23, 683–747 (2005).

    Article  CAS  Google Scholar 

  7. Biernacki, K., Prat, A., Blain, M. & Antel, J.P. J. Neuropathol. Exp. Neurol. 60, 1127–1136 (2001).

    Article  CAS  Google Scholar 

  8. Prat, A., Biernacki, K. & Antel, J.P. J. Autoimmun. 24, 119–124 (2005).

    Article  CAS  Google Scholar 

  9. Liang, S.C. et al. J. Exp. Med. 203, 2271–2279 (2006).

    Article  CAS  Google Scholar 

  10. Chung, Y. et al. Cell Res. 16, 902–907 (2006).

    Article  CAS  Google Scholar 

  11. Zheng, Y. et al. Nature 445, 648–651 (2007).

    Article  CAS  Google Scholar 

  12. Komiyama, Y. et al. J. Immunol. 177, 566–573 (2006).

    Article  CAS  Google Scholar 

  13. Uyttenhove, C. & Van, S.J. Eur. J. Immunol. 36, 2868–2874 (2006).

    Article  CAS  Google Scholar 

  14. Wosik, K. et al. J. Neurosci. 27, 9032–9042 (2007).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by funding from the Multiple Sclerosis Society of Canada (MSSC) and from the Canadian Fund for Innovation to A.P. The animal studies were supported through grants from the US National MS Society and the Swiss National Science Foundation (B.B.). H.K., I.I., A.D.-D. and R.C. hold studentships from the MSSC and the Canadian Institutes of Health Research (CIHR)/Strategic Training Initiative in Health Research Neuroinflammation Training Program. K.K. has a fellowship from the Center for Neurosciences in Zurich. N.A. holds a CIHR Senior Research Fellowship Phase 2. B.B. is a Neuroscience Scholar of the US National MS Society. A.P. is a Research Scholar from the Fonds de la Recherche en Santé du Québec, and holds the Donald Paty Career Award of the MSSC. We thank I. Gutcher, S. Haak, D. Pasichnyk and J. Laganière for their excellent technical assistance. We are grateful to V.K. Kuchroo (Harvard Medical School), who kindly provided the 2D2 mice, and to J.P. Antel (McGill University) for providing assistance and human tissue.

Author information

Authors and Affiliations

Authors

Contributions

H.K. conducted most of the experiments; K.K. performed and analyzed animal studies; I.I. and A.D.-D. contributed to immunostaining and in vitro protocols; R.C. assisted with confocal microscopy and performed some EAE experiments; M.B. assisted with BBB-EC isolation and culture; F.G. performed the killing assay; N.A. provided critical input on data analysis; B.B. designed and supervised the animal studies; H.K. and A.P. designed the study, analyzed the data and wrote the manuscript; A.P. secured the funding.

Corresponding author

Correspondence to Alexandre Prat.

Supplementary information

Supplementary Text and Figures

Supplementary Methods (PDF 82 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kebir, H., Kreymborg, K., Ifergan, I. et al. Human TH17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation. Nat Med 13, 1173–1175 (2007). https://doi.org/10.1038/nm1651

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nm1651

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing