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    Early cell signalling during chemokine-induced T cell migration

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    Responsable du projet : Clotilde Randriamampita

    Contact: clotilde.randriamampita@inserm.fr – Tel : +33-40-51-65-60

     

     Objectif

    Upon chemokine stimulation, T cells rapidly polarize and start to migrate. These steps are necessary for T cell entry into lymph node but also for intranodal migration that favors their interaction with antigen-presenting cells. We aim to determine the signaling event triggered by chemokine which induce the asymmetrical deformation of the cells and thereafter their migration. These issues are addressed by classical cell biology approaches but also by dynamic cell imaging technology coupled to the use of biosensor. We can therefore investigate signaling events at the cellular even subcellular level, with a good temporal resolution.

     

    Composition of the group

    In 2019, the group is of Morgane Simao (PhD student, Université Paris Descartes) and Fabienne Régnier (Technician INSERM).

     

    Research interests

    Few years ago, we identified cAMP as a key molecule involved in the sensitization of T cells upon adhesion to antigen presenting cells (Conche, Immunity 2009). More recently, we demonstrated that this messenger is also involved prior to T cell adhesion as an important factor for T cell polarization and migration upon chemokine stimulation. By performing live imaging analysis using bisosensors such as TEpacVV based on FRET, we can measure cAMP at the subcellular level upon chemokine stimulation, such as CXCL12, and correlate these variations to morphological changes. Distribution of actin cytoskeleton is simultaneously recorded and its distribution correlated to cAMP measurements (figure below). In parallel with develop some Traction Force Microscopy experiments in order to measure the forces applied on the substrate by the cell upon migration. These measures will be performed simultaneously with signaling event recording.

     

     Main publications

    • Guedj, C., Abraham, N., Jullié, D., Randriamampita, C. (2016) T cell adhesion triggers an early signaling pole distal to the immune synapse. J Cell Sci. 129: 2526-2537
    • Randriamampita, C. and Lellouch A. C. Imaging early signalling events in T lymphocytes with fluorescent biosensors Biotechnology Journal 2014; 9: 203-12
    • Hauck, F., Randriamampita, C., Martin, E., Gerart, S., Lambert, N., Lim, A., Soulier, J., Maciorowski, Z., Touzot, F., Moshous, D., Quartier-dit-Maire, P., Heritier, S., Blanche, S., Fraitag, S., Brousse, N., Veillette, A., Hivroz, C., Fischer, A., Latour, S. and Picard, C. Primary T-Cell Immunodeficiency with Immunodysregulation Caused by Autosomal Recessive LCK Deficiency. J Allergy Clin Immunol 2012; 130(5):1144-1152.e11.
    • Conche, C., Boulla, G., Trautmann, A., Randriamampita, C. T cell adhesion primes antigen receptor-induced calcium responses through a transient rise in adenosine 3',5'-cyclic monophosphate Immunity 2009; 30(1):33-43
    • Randriamampita, C., Mouchacca, P., Malissen, B., Marguet, D., Trautmann, A., Lellouch, A. C. A Novel ZAP-70 Dependent FRET Based Biosensor Reveals Kinase Activity at both the Immunological Synapse and the Antisynapse PLoS ONE 2008; 3:e1521

     

     

     

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