Skip to main content
SpringerLink
Log in

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

  • Brief Communication
  • Published:

From Nature Medicine

View current issue Submit your manuscript

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, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

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

  1. Neuroimmunology Unit, Center for the Study of Brain Diseases, Centre Hospitalier de l'Université de Montréal–Notre-Dame Hospital, 1560 Sherbrooke Street East, Montreal, H2L 4M1, Quebec, Canada

    Hania Kebir, Igal Ifergan, Aurore Dodelet-Devillers, Romain Cayrol, Monique Bernard, Nathalie Arbour & Alexandre Prat

  2. Neurology Department, Division of Neuroimmunology, University of Zurich, Winterthurerstrasse 190, Zurich, 8057, Switzerland

    Katharina Kreymborg & Burkhard Becher

  3. Department of Medicine, Division of Neurology, University of Alberta, Alberta, Edmonton, T6G 2G3, Canada

    Fabrizio Giuliani

Authors
  1. Hania Kebir
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Katharina Kreymborg
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Igal Ifergan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Aurore Dodelet-Devillers
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Romain Cayrol
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Monique Bernard
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Fabrizio Giuliani
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Nathalie Arbour
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Burkhard Becher
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Alexandre Prat
    View author publications

    You can also search for this author in PubMed Google Scholar

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

  • Springer Nature America, Inc.

This article is cited by

Search

Navigation