The regional distribution of resident immune cells shapes distinct immunological environments along the murine epididymis

The epididymis constitutes an important transition zone for post-testicular sperm maturation and storage. As the organ consists of a single convoluted duct, inflammation-associated tissue damage has a severe impact on fertility. In order to clarify the reasons for region-specific differences in the intensity of immune responses observed in a mouse model of acute bacterial epididymitis, we investigated the heterogeneity of resident immune cell populations within the epididymis under physiological conditions by scRNASeq analysis of extravascular CD45 ⁺ cells. 12 distinct immune cell subsets were identified, displaying substantial differences in distribution along the epididymis. Several distinct subsets of macrophages constituted the majority of these cells. Crucially, the proximal and distal regions showed striking differences in their immunological landscapes. These findings indicate that resident immune cells are strategically positioned along the epididymal duct, potentially providing different immunological environments required for sperm maturations and elimination of pathogens ascending the urogenital tract.