T cells; single cell; multiple sclerosis; migration; microfluidics; heterogeneity
Amstad Andrea, Coray Mali, Frick Corina, Barro Christian, Oechtering Johanna, Amann Michael, Wischhusen Jörg, Kappos Ludwig, Naegelin Yvonne, Kuhle Jens, Mehling Matthias (2020), Growth differentiation factor 15 is increased in stable MS, in Neurology - Neuroimmunology Neuroinflammation
, 7(2), e675-e675.
Naegelin Y., Rasenack M., Andelova M., Von Felten S., Fischer-Barnicol B., Amann M., Mehling M., Kappos L., Sprenger T., Derfuss T. (2018), Shortening the washout to 4 weeks when switching from natalizumab to fingolimod and risk of disease reactivation in multiple sclerosis, in Multiple Sclerosis and Related Disorders
, 25, 14-20.
Frick Corina, Dettinger Philip, Renkawitz Jörg, Jauch Annaïse, Berger Christoph T., Recher Mike, Schroeder Timm, Mehling Matthias (2018), Nano-scale microfluidics to study 3D chemotaxis at the single cell level, in PLOS ONE
, 13(6), e0198330-e0198330.
Bigler Marc B., Hirsiger Julia R., Recher Mike, Mehling Matthias, Daikeler Thomas, Berger Christoph T. (2018), Varicella Zoster Virus-Specific T Cell Responses in Untreated Giant Cell Arteritis: Comment on the Article by England et al, in Arthritis & Rheumatology
, 70(2), 318-320.
Vaahtomeri Kari, Vaahtomeri Kari, Brown Markus, Hauschild Robert, De Vries Ingrid, Leithner Alexander Franz, Mehling Matthias, Kaufmann Walter Anton, Sixt Michael (2017), Locally Triggered Release of the Chemokine CCL21 Promotes Dendritic Cell Transmigration across Lymphatic Endothelia, in Cell Reports
, 19(5), 902-909.
Schwarz Jan, Bierbaum Veronika, Merrin Jack, Frank Tino, Hauschild Robert, Bollenbach Tobias, Bollenbach Tobias, Tay Savaş, Tay Savaş, Sixt Michael, Mehling Matthias, Mehling Matthias (2016), A microfluidic device for measuring cell migration towards substrate-bound and soluble chemokine gradients, in Scientific Reports
, 6, 36440.
Sarah Dimeloe, Matthias Mehling, Corina Frick, Jordan Loeliger, Glenn R. Bantug, Ursula Sauder, Marco Fischer, Réka Belle, Leyla Develioglu, Savas Tay, Anja Langenkamp, Christoph Hess (2016), The Immune-Metabolic Basis of Effector Memory CD41 T Cell Function under Hypoxic Conditions, in The Journal of Immunology
, 2016(196), 106-114.
To mount a protective immune response, a highly orchestrated positioning of lymphocytes is essential. This intricate process is enabled by a complex and precisely regulated interplay of chemokines/chemokine receptors and adhesion molecules, directing migration of T cells to and within non-lymphoid and secondary lymphoid tissues. Conversely, migration of autoreactive lymphocytes is fundamental to the pathogenesis of autoimmune diseases, such as multiple sclerosis (MS). Most of our insight into T cell migration is based on the monitoring of bulk cell populations in animal models. For human T cells, a relatively limited set of migration-characteristics have been recapitulated in vitro, again mostly by using bulk cell populations. While important understanding of mechanisms underlying T cell migration derives from these studies, potential heterogeneity of migration between individual cells is not interrogated using this approach. Also, clinical samples containing only small numbers of T cells are not amenable for analysis using classical in vitro migration assays. Specifically, understanding the migration characteristics of CSF-derived T cells in MS patients -the closest routinely accessible approximation to pathogenic cells in this disease- would be of particular interest.In recent years, introduction of microfabrication technologies resulted in the generation of so-called microfluidic devices, which allow monitoring of cells on a single-cell level with high spatio-temporal resolution. Together with the microfluidics group at ETH Zurich, we have developed a microfluidic device specifically designed to studying the migration characteristics of primary human T cells. This device allows the highly precise build-up of chemokine gradients. Characterizing migration properties of individual human CD4+ memory T cells (CD4 TM) ex vivo, we have already established the proof of concept that this technique can overcome previous limitations of standard migration assays.The General Aim of this proposal is to explore the migration characteristics of primary human T cells from blood and/or cerebrospinal fluid from patients with MS and controls on a single cell level. Linking this information with clinical information carries the potential to establish a functional immune profile comprising data on T cell parameters with an established role in disease pathogenesis.