Project Details
Projekt
Macrophage-epithelial cell interactions in the epididymis during homeostasis and inflammation
Subject Area
Reproductive Medicine, Urology
Term
since 2024
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 515636567
The epididymis is essential for post-testicular maturation of spermatozoa that undergo complex spatial biochemical processes during their passage through the duct. The organ is divided into initial segment, caput, corpus and cauda regions in mice. Each region is characterized by distinct cellular compositions and functions that create a unique luminal milieu necessary for sperm maturation. The epithelium is composed of different cell types that direct this sequential maturation. The epididymis faces contrasting immunological challenges at the opposing ends of its duct. At the proximal part (IS, caput) immunological tolerance is required towards immunogenic spermatozoa, whereas the distal end (cauda) mounts efficient immunity against pathogens ascending from the urethra. In support, infectious and inflammatory cues cause a strong immunoreaction and associated tissue damage only in the cauda, whereas the caput and initial segment show no reaction. Studies have unveiled a diverse network of tissue-resident macrophages within the epithelial compartments with striking region-specific differences in their distribution and transcriptional profiles. We hypothesize that reciprocal macrophage - epithelial cell crosstalk is crucial for epididymal homeostasis and the adequate induction and tuning of immunity towards invading pathogens. Therefore, this application aims to dissect molecular interactions between epididymal epithelial cells and intraepithelial macrophages along the spatial organization of the epididymis how this governs organ function in steady-state and infectious disease. As part of the FOR 'INFINITE' application in a highly collaborative manner, we will use spatial transcriptomics, CODEX enabled single-cell resolution proteomics, scRNA-seq analysis and bioinformatics as well as macrophage depletion models to dissect spatially restricted macrophage programs and macrophage - epithelial cell circuits on the transcriptional and phenotypic level to better understand the maintenance of the unique inflammatory gradient along the ductal axis of the epididymis.
DFG Programme
Research Units
