Immune-cell interactions with endothelial cells and pericytes at the blood-brain-barrier: Mechanisms and consequences

    Our project investigates mechanisms how lymphocytes breach the blood-brain-barrier and contribute to CNS inflammation. In the first part, we aim to reveal the key influencing factors as well as underlying mechanisms of immune cell-mediated brain endothelial barrier disruption under static and under flow conditions. In the second part, we aim to study the role of pericytes as cellular constituents of the blood-brain-barrier during the process of immune cell transmigration in the context of CNS autoimmunity, especially with regard to potential interactions with autoreactive T cells shaping T cell activity and migratory behaviour.

    Research area: Neuroimmunology

    Prof. Dr. med. Heinz Wiendl
    Prof. Dr. med. Luisa Klotz (since 07/2016)

    Funding period: July 2012 - June 2024

    • Publications

      Original articles

      • Klotz L, Eschborn M, Lindner M, Liebmann M, Herold M, Janoschka C, Garrido BT, Schulte-Mecklenbeck A, Gross CC, Breuer J, Hundehege P, Posevitz V, Pignolet B, Nebel G, Glander S, Freise N, Austermann J, Wirth T, Campbell GR, Schneider-Hohendorf T, Eveslage M, Brassat D, Schwab N, Loser K, Roth J, Busch KB, Stoll M, Mahad DJ, Meuth SG, Turner T, Bar-Or A, Wiendl H (2019) Teriflunomide treatment for multiple sclerosis modulates T cell mitochondrial respiration with affinity-dependent effects. Sci. Transl. Med. 11(490).
      • Breuer J, Schneider-Hohendorf T, Ostkamp P, Herich S, Rakhade S, Antonijevic I, Klotz L, Wiendl H & Schwab N (2019) VLA-2 blockade in vivo by vatelizumab induces CD4+FoxP3+ regulatory T cells. Int. Immunol. 31(6):407-412.
      • Liebmann M, Hucke S, Koch K, Eschborn M, Ghelman J, Chasan AI, Glander S, Schädlich M, Kuhlencord M, Daber NM, Eveslage M, Beyer M, Dietrich M, Albrecht P, Stoll M, Busch KB, Wiendl H, Roth J, Kuhlmann T & Klotz L (2018) Nur77 serves as a molecular brake of the metabolic switch during T cell activation to restrict autoimmunity. Proc. Natl. Acad. Sci. U. S. A. 115(34):E8017-E8026.
      • Lindner M, Klotz L & Wiendl H (2018) Mechanisms underlying lesion development and lesion distribution in CNS autoimmunity. J. Neurochem. 146(2):122-132.
      • Lohmann L, Janoschka C, Schulte-Mecklenbeck A, Klinsing S, Kirstein L, Hanning U, Wirth T, Schneider-Hohendorf T, Schwab N, Gross CC, Eveslage M, Meuth SG, Wiendl H & Klotz L (2018) Immune cell profiling during switching from natalizumab to fingolimod reveals differential effects on systemic immune-regulatory networks and on trafficking of Non-T cell populations into the cerebrospinal fluid-results from the ToFingo successor study. Front. Immunol. 9:1560.
      • Albrecht S, Fleck AK, Kirchberg I, Hucke S, Liebmann M, Klotz L, Kuhlmann T. (2017) Activation of FXR pathway does not alter glial cell function. J Neuroinflammation 14(1):66. (doi: 10.1186/s12974-017-0833-6)
      • Song J, Zhang X, Buscher K, Wang Y, Wang H, Di Russo J, Li L, Lütke-Enking S, Zarbock A, Stadtmann A, Striewski P, Wirth B, Kuzmanov I, Wiendl H, Schulte D, Vestweber D & Sorokin L (2017) Endothelial Basement Membrane Laminin 511 Contributes to Endothelial Junctional Tightness and Thereby Inhibits Leukocyte Transmigration. Cell Rep. 18(5):1256-1269.
      • Gross CC, Schulte-Mecklenbeck A, Hanning U, Posevitz-Fejfar A, Korsukewitz C, Schwab N, Meuth SG, Wiendl H & Klotz L (2016) Distinct pattern of lesion distribution in multiple sclerosis is associated with different circulating T-helper and helper-like innate lymphoid cell subsets. Mult. Scler. 23(7):1025-1030.
      • Klotz L, Kuzmanov I, Hucke S, Gross CC, Posevitz V, Dreykluft A, Schulte-Mecklenbeck A, Janoschka C, Lindner M, Herold M, Schwab N, Ludwig-Portugall I, Kurts C, Meuth SG, Kuhlmann T & Wiendl H (2016) B7-H1 shapes T-cell–mediated brain endothelial cell dysfunction and regional encephalitogenicity in spontaneous CNS autoimmunity. Proc. Natl. Acad. Sci. 113(41):E6182-E6191.
      • Kuzmanov I, Herrmann AM, Galla HJ, Meuth SG, Wiendl H & Klotz L (2016) An in vitro model of the blood-brain barrier using impedance spectroscopy: A focus on T cell-endothelial cell interaction. J. Vis. Exp.118.
      • Mykicki N, Herrmann AM, Schwab N, Deenen R, Sparwasser T, Limmer A, Wachsmuth L, Klotz L, Kohrer K, Faber C, Wiendl H, Luger TA, Meuth SG & Loser K (2016) Melanocortin-1 receptor activation is neuroprotective in mouse models of neuroinflammatory disease. Sci. Transl. Med. 8: 362ra146-362ra146.
      • Herold M, Posevitz V, Chudyka D, Hucke S, Groß C, Kurth F, Leder C, Loser K, Kurts C, Knolle P, Klotz L, Wiendl H (2015) Selectively Controls TH17 Differentiation and Central Nervous System Autoimmunity via a Novel Non-PD-1-Mediated Pathway. J Immunol. 195(8):3584-95. (doi: 10.4049/jimmunol.1402746. Epub 2015 Sep 16.)
      • Schneider-Hohendorf T, Rossaint J, Mohan H, Böning D, Breuer J, Kuhlmann T, Gross CC, Flanagan K, Sorokin L, Vestweber D, Zarbock A, Schwab N, Wiendl H (2014) VLA-4 blockade promotes differential routes into human CNS involving PSGL-1 rolling of T cells and CAM-adhesion of TH17 cells. J Exp Med 211 (9): 1833-1846.  (doi: 10.1084/jem.20140540)

      Reviews

      • Wiendl H, Gross CC (2013) Modulation of IL-2Rα with daclizumab for treatment of multiple sclerosis. Nature Rev Neurol 9: 394-404.
      Reviews
      • Wiendl H, Gross CC (2013) Modulation of IL-2Rα with daclizumab for treatment of multiple sclerosis. Nature Rev Neurol 9: 394-404.