The immunology of blood: connecting the dots at the neurovascular interface

An Author Correction to this article was published on 07 July 2020

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Katerina Akassoglou recounts how her work on the mechanisms and functions of blood leaks in the brain led to the discovery of fibrin-targeting immunotherapy.

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Fig. 1: Fibrin mechanisms and functions in neuroinflammation.

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  • 07 July 2020

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

References

  1. 1.

    Rindfleisch, E. Archiv Pathol. Anat. Physiol. 26, 474–483 (1863).

    Article  Google Scholar 

  2. 2.

    Petersen, M. A., Ryu, J. K. & Akassoglou, K. Nat. Rev. Neurosci. 19, 283–301 (2018).

    CAS  Article  Google Scholar 

  3. 3.

    Davalos, D. & Akassoglou, K. Semin. Immunopathol. 34, 43–62 (2012).

    CAS  Article  Google Scholar 

  4. 4.

    Ryu, J. K. et al. Nat. Immunol. 19, 1212–1223 (2018).

    CAS  Article  Google Scholar 

  5. 5.

    Keffer, J. et al. EMBO J. 10, 4025–4031 (1991).

    CAS  Article  Google Scholar 

  6. 6.

    Vilcek, J. Love and Science: A Memoir (Seven Stories Press, 2016).

  7. 7.

    Cross, A. H., Vincent, A. & Racke, M. K. J. Neuroimmunol. 58, 117–120 (1995).

    CAS  Article  Google Scholar 

  8. 8.

    Probert, L., Akassoglou, K., Pasparakis, M., Kontogeorgos, G. & Kollias, G. Proc. Natl Acad. Sci. USA 92, 11294–11298 (1995).

    CAS  Article  Google Scholar 

  9. 9.

    Akassoglou, K., Probert, L., Kontogeorgos, G. & Kollias, G. J. Immunol. 158, 438–445 (1997).

    CAS  PubMed  Google Scholar 

  10. 10.

    Kassiotis, G. et al. Eur. J. Immunol. 29, 912–917 (1999).

    CAS  Article  Google Scholar 

  11. 11.

    Akassoglou, K. et al. Am. J. Pathol. 153, 801–813 (1998).

    CAS  Article  Google Scholar 

  12. 12.

    Tang, L., Ugarova, T. P., Plow, E. F. & Eaton, J. W. J. Clin. Invest. 97, 1329–1334 (1996).

    CAS  Article  Google Scholar 

  13. 13.

    Tsirka, S. E., Gualandris, A., Amaral, D. G. & Strickland, S. Nature 377, 340–344 (1995).

    CAS  Article  Google Scholar 

  14. 14.

    Akassoglou, K., Kombrinck, K. W., Degen, J. L. & Strickland, S. J. Cell Biol. 149, 1157–1166 (2000).

    CAS  Article  Google Scholar 

  15. 15.

    Bugge, T. H. et al. Cell 87, 709–719 (1996).

    CAS  Article  Google Scholar 

  16. 16.

    Akassoglou, K., Yu, W.-M., Akpinar, P. & Strickland, S. Neuron 33, 861–875 (2002).

    CAS  Article  Google Scholar 

  17. 17.

    Akassoglou, K. et al. Proc. Natl Acad. Sci. USA 101, 6698–6703 (2004).

    CAS  Article  Google Scholar 

  18. 18.

    Paterson, P. Y. Fed. Proc. 35, 2428–2434 (1976).

    CAS  PubMed  Google Scholar 

  19. 19.

    Sachs, B. D. et al. J. Cell Biol. 177, 1119–1132 (2007).

    CAS  Article  Google Scholar 

  20. 20.

    Cortes-Canteli, M. et al. Neuron 66, 695–709 (2010).

    CAS  Article  Google Scholar 

  21. 21.

    Montagne, A. et al. Nat. Med. 24, 326–337 (2018).

    CAS  Article  Google Scholar 

  22. 22.

    Pous, L. et al. Nat. Commun. 11, 630 (2020).

    CAS  Article  Google Scholar 

  23. 23.

    Akassoglou, K. & Strickland, S. Biol. Chem. 383, 37–45 (2002).

    CAS  Article  Google Scholar 

  24. 24.

    Schachtrup, C. et al. Proc. Natl Acad. Sci. USA 104, 11814–11819 (2007).

    CAS  Article  Google Scholar 

  25. 25.

    Petersen, M. A. et al. Neuron 96, 1003–1012.e7 (2017).

    CAS  Article  Google Scholar 

  26. 26.

    Schachtrup, C. et al. J. Neurosci. 30, 5843–5854 (2010).

    CAS  Article  Google Scholar 

  27. 27.

    Adams, R. A. et al. J. Exp. Med. 204, 571–582 (2007).

    CAS  Article  Google Scholar 

  28. 28.

    Ugarova, T. P. et al. Biochemistry 42, 9365–9373 (2003).

    CAS  Article  Google Scholar 

  29. 29.

    Flick, M. J. et al. J. Clin. Invest. 113, 1596–1606 (2004).

    CAS  Article  Google Scholar 

  30. 30.

    Davalos, D. et al. Nat. Commun. 3, 1227 (2012).

    Article  Google Scholar 

  31. 31.

    Davalos, D. et al. Ann. Neurol. 75, 303–308 (2014).

    CAS  Article  Google Scholar 

  32. 32.

    Lee, N. J. et al. Brain 141, 1637–1649 (2018).

    Article  Google Scholar 

  33. 33.

    Ryu, J. K. et al. Nat. Commun. 6, 8164 (2015).

    Article  Google Scholar 

  34. 34.

    Merlini, M. et al. Neuron 101, 1099–1108.e6 (2019).

    CAS  Article  Google Scholar 

  35. 35.

    Mendiola, A. S. et al. Nat. Immunol. 21, 513–524 (2020).

    CAS  Article  Google Scholar 

  36. 36.

    Coller, B. S., Anderson, K. M. & Weisman, H. F. Haemostasis 26 (Suppl. 4), 285–293 (1996).

    CAS  PubMed  Google Scholar 

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Acknowledgements

I am especially grateful to all my current and former laboratory members for their creativity, grit and exceptional contributions. I thank my mentors, collaborators and colleagues for their enthusiasm and continued support. Thanks to Hans Lassmann, Sidney Strickland, Jay L. Degen, George Kollias, Moses V. Chao, Mark A. Petersen and Kathryn Claiborn for critical reading of this manuscript. K.A. is currently supported by NIH/NINDS R35 NS097976, NIH/NIA RF1 AG064926, Department of Defense MS160082, the Dagmar Dolby Family Fund, Edward and Pearl Fein and the Simon Family Trust. Lastly, I am grateful to the University of California, San Diego; Gladstone Institutes; and the University of California, San Francisco for promoting a culture of discovery and innovation.

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Correspondence to Katerina Akassoglou.

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Competing interests

K.A. is the scientific founder and advisor of Therini Bio, Inc. K.A. is an inventor on The Regents of the University of California issued patents US7807645, US8569242, US8877195 and US8980836 covering fibrin antibodies; a co-inventor on The Regents of the University of California and Gladstone Institutes pending patent applications U.S. 15/943,474 and EP 15735033.1 covering fibrin assays of microglia activation; and a co-inventor on Gladstone Institutes issued patent US9669112 covering fibrin in vivo models and US10451611 and pending patent applications U.S. 16/572,365 and EP 15735284.05 covering in vitro fibrin assays. Her interests are managed in accordance with the Gladstone Institutes’ conflict of interest policy.

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Akassoglou, K. The immunology of blood: connecting the dots at the neurovascular interface. Nat Immunol 21, 710–712 (2020). https://doi.org/10.1038/s41590-020-0671-z

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