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Functional dissection of metabolic checkpoints in lymph node fibroblastic reticular cells

Project description

Local energy landscape and lymph cell activation

The lymph system helps rid the body of toxins, waste and other unwanted materials. Fibroblastic reticular cells play an important role in lymph system function and immunity. They help coordinate the migration and positioning of lymph cells and also produce essential factors for homeostasis and immune activation. Currently, it is not clear how these critical cells are activated. The EU-funded FRC BioEnergetics project is focusing on metabolic states and the energy landscape during homeostasis and the induction of immune responses. More globally, scientists will evaluate whether local metabolic state affects the global immune response in the same ways. Inflammation and immunity are key players in numerous conditions so outcomes will have broad-sweeping impact.

Objective

Induction and regulation of optimal immune responses depends on the proper functioning of fibroblastic reticular cells (FRCs) of secondary lymphoid organs (SLOs). Energy balance maintained through the choice of ideal metabolic pathways critically influences the performance of immune cells. Currently, the bioenergetic demands of FRCs and how they impinge on their function remain elusive. The overarching goal of this project is to decipher the bioenergetic needs of FRCs in homeostasis and during inflammation and to uncover the critical immunological signals involved in the metabolic shift of FRCs that underpin immune activation. Combination of state-of-the-art models for in vivo FRC targeting, novel methods from quantitative systems biology and molecular perturbation analysis will be utilized to reveal the metabolic landscape supporting optimal FRC function and the induction of immune responses. Specifically, “FRC BioEnergetics” will determine: The bioenergetic profile of homeostatic vs. inflammatory FRCs and identify the metabolic switching necessary to support the transition to immune-activated state of FRCs (Aim 1); Identify the immunological signals that trigger metabolic switching necessary to support FRC activation (Aim 2) and Determine to what extent metabolic regulation of FRC function impacts on global immune responsiveness (Aim 3). The focus of the multidisciplinary research program on metabolic regulation of FRC function as central means for the control of immune responsiveness will reveal novel principles underlying immune homeostasis and immunity. “FRC BioEnergetics” will expand our knowledge of the intricate metabolic regulation of immune cell function, with the final goal to provide novel options to modulate immune responses by targeting FRC metabolism and deliver better immunotherapeutic strategies against infection, cancer and autoimmune disorders.

Fields of science (EuroSciVoc)

Programme(s)

Topic(s)

Funding Scheme

MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

(opens in new window) H2020-MSCA-IF-2018

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Coordinator

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Net EU contribution
€ 162 806,40
Address
HOFGARTENSTRASSE 8
80539 MUNCHEN
Germany
Region
Berlin Berlin Berlin
Activity type
Research Organisations
Links
Total cost
€ 162 806,40