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Dynamic T cell centrosomal protein network controls exosome-mediated anti-pathogen activity in dendritic cells: FOSTER interactome

19th national competition for scientific and technical research

Intercellular Dialogue and Interactome: Pathological Implications

Senior Researcher : Francisco Sánchez Madrid

Research Centre or Institution : Universidad Autónoma de Madrid.

Abstract

The present proposal addresses three specific aims under the following headings. 

1. Control of exosomal sorting of cellular components in T cells by FOSTER interactome folding and processing activities and exosome transfer upon synaptic challenge by Dendritic Cells (DC). T cells with deregulated FOSTER-interactome folding activities show a differential composition in the lipid and protein species detected in exosomes (Texo). We have used specific cryoelectron microscopy protocols to study the organization of the endolysosomal compartment. The changes in lipid composition of T cells upon deregulation of the FOSTER interactome have been profiled, which involve the tubulin cytoskeleton and associated kinesins.

2. Regulation of the metabolic and transcriptional changes induced in Dendritic Cells by synaptic challenges and exosome transfer through the folding activities at the centrosome region in T cells. The failure in the dynamic reorganization of mitochondria and in their functional fate has been shown by advanced optical fluorescence videomicroscopy techniques. We have corroborated the role of FOSTER components by using chemical inhibitors affecting ribosome and proteasome function. The changes in the Immune synapse formation involve a differential secretion of Texo, which comprise, in turn, different components that their counterpart control Texo.

3. Role of FOSTER interactome in the exosomal sorting of mitochondrial components and the subsequent induction of an Immunogenic Profile in DC to regulate anti-pathogen responses. We have determined the specific Immunogenic Profile of DCs upon the uptake of T cell of  exosomes derived from T cells and DCs in several animal models of infection with virus and intracellular bacteria. We have also established methods based on high-resolution TIRF microscopy to visualize the exosome composition.

 

Scientific Production
 
Magazine Articles 25
Communications at national conferences 10
Communications at international conferences 4

 

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