Project Details
Projekt
Role of macrophage-derived Apolipoprotein E in the regulation of small intestinal macrophage longevity and function (Project 4 of the FOR5775 MagNet)
Applicant
Professor Dr. Andreas Schlitzer
Subject Area
Immunology
Cell Biology
Cell Biology
Term
since 2025
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 533863915
Macrophages are heterogeneous and placed in intricate communities throughout the different functionally specialized anatomical layers of the small intestine. Their overall anatomical placement and, to a limited extent, their cellular communities have been elucidated; however, how different macrophage subsets integrate and modulate their direct cellular environment during homeostasis remains largely unknown. Among other cells, a close interaction of intestinal neurons and macrophages has been shown by us and others. We and others have recently identified Apolipoprotein E (ApoE) has a critical constituent for the development and longevity of tissue-resident macrophages in the lung and the brain. However, the role of ApoE and its receptors for macrophage neuron crosstalk within the lamina propria of the small intestine has yet to be studied. Thus, we hypothesize that macrophage-derived ApoE is a crucial spatial organizer of macrophage-centric cellular communities, controls maturation of the enteric neuron network thus is a crucial component of maintaining small intestinal organ function. To address these questions, we have formulated the following aims: Aim 1: To investigate the ontogeny, spatial tissue niche and associated transcriptomic programs of murine small intestinal macrophage subsets from birth to adulthood. Aim 2: To dissect the macrophage-centric spatial, functional, and metabolic consequences of ApoE deficiency in the postnatally developing homeostatic small intestine. Aim 3: To mechanistically interrogate the functional impact of macrophage-derived ApoE in vivo and ex vivo.
DFG Programme
Research Units
