Immune regulation at the CNS barriers and in the CNS: role of immune cell trafficking


Infiltration of immune cells into the central nervous system (CNS) is one major hallmark of multiple sclerosis (MS) pathology. Natalizumab is a therapeutic integrin for to treat MS that inhibits the very late antigen (VLA)-4. In rare cases, therapy is accompanied by a progressive multiple leukencephalopathy, a rare but potentially fatal brain infection. By extending the dosing interval of natalizumab, the PML incidence in MS patients can be reduced by 90%, whereas efficacy seems preserved. We hypothesize that a cellular subtype preferentially benefits from extended natalizumab interval dosing and resumes CNS immune surveillance in patients receiving extended interval dosing. We will investigate the relationship between therapeutic integrin engagement and selectin expression for lymphocyte surveillance function with implications for virus control. Furthermore, we will analyze the antigen specificity of MCAM+ and CCR5high CNS-infiltrating T cells to decipher their exact roles in CNS immune surveillance versus inflammation. Lastly, we will transfer the generated molecular and cellular concepts of adaptive CNS immunity to the coagulation system. There we will analyze the contribution of leukocyteplatelet aggregates to adaptive CNS immunity in the context of MS. In other words, we will tackle these questions:

      1. What is the role of CNS-patrolling CD4 vs CNS-resident CD8 lymphocytes in CNS immune surveillance, MS pathology and viral control with decreasing VLA-4 inhibition?
      2. Why do certain immune cells specifically infiltrate the CNS?
      3. Could immune cells performing (excessive) CNS immune surveillance contribute to MS pathology or even pathogenesis?
      4. Is there a direct mechanistic link between integrin-β1 engagement by natalizumab, T-cell activation and L-selectin shedding?
      5. What is the tole of Role of platelet-leukocyte-aggregates in MS pathology and progression?

      Herich et al., Brain 2019

      Herich et al., Brain 2019


Principal Investigators

Univ.-Prof. Dr. rer. nat. Nicholas Schwab
Klinik für Neurologie mit Institut für Translationale Neurologie

Prof. Dr. med. Alexander Zarbock
Klinik für Anästhesiologie und Intensivmedizin


Mon, 09/05/2022
Scientific Retreat including public Webinar
Muenster. For the first time after a longer pandemic-related break, the SFB 128 will host an onsite retreat. On Thursday and Friday, 23 and 24 June, the participating scientists will meet in Muenster to present the current status and developments of their projects. The event is also an opportunity for the exchange and the discussion […]...more
Wed, 19/01/2022
One drug – different effects: Metabolism of immune cells influences mode of action and could be an indicator for side effects
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Tue, 14/12/2021
Save the date: 2nd Inflammation & Imaging Symposium
Münster. Save the date: 12-14 September 2022! We cordially invite you to join this international symposium, jointly organized by the research networks CRC 1450, CRC 1009, CRC 1348, CRU 342, CRC/TR 128 and the Cells in Motion Interfaculty Centre at the University of Münster. At the same time, we will officially open the new research […]...more