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


Wed, 23/08/2023
Neurology Webinar on human brain T cells in health and multiple sclerosis
Muenster. The SFB 128 is happy welcome Joost J.F.M. Smolders, MD, PhD , head of MS Center ErasMS and Neuroimmunology Brain (NIB) Research Group at the Department of Immunology of the Erasmus University Medical Center (Erasmus MC), as lecturer at the Muenster Neurology Webinar. His talk is entitled “Unique features of human brain T cells […]...more
Thu, 03/08/2023
Neurology Webinar – How much gut needs the brain
Muenster. In December 2023, Prof. Anne-Katrin Pröbstel, Head of the Interdisciplinary Autoimmune Clinic at the University Hospital of Basel, will visit Muenster to give insights into the microbiota-immune crosstalk in neuroonflammation. Her presentation – which ois part of the Muenster Neurology Webinar – will be live-streamed. Time: Wednesday, December 13, 5:15 p.m. Place: Online at […]...more
Thu, 02/02/2023
3rd Inflammation & Imaging Symposium in Münster, 11-13 September 2023
Application has opened! We cordially invite you to join this international conference and discuss the latest developments in research on inflammation and the imaging of the immune system with us. The symposium is organised by eight research networks from the University of Münster – CRU 342, CRC 1009, CRC 1450, CRC/TR 128, CRC/TR 332, InFlame, […]...more