Functional dissection of metabolic checkpoints in lymph node fibroblastic reticular cells

2026-07-22

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.

Germany

2026-02-01