Project Details
Projekt
Macrophage dependent inflammation in the ageing testis
Applicants
Dr. Sudhanshu Bhushan; Professor Dr. Christian Schulz
Subject Area
Reproductive Medicine, Urology
Term
since 2024
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 515636567
Age is an independent risk factor for the functional and structural decline of the male reproductive system. Ageing is associated with chronic inflammation, fibrosis, cell death, and a senescence phenotype of somatic cells, which leads to subfertility and exerts profound effects on the normal function of the testis. In this proposal, we aim to investigate age-induced changes in macrophage immunity and its impact on testicular function and inflammatory response. Macrophages are the most abundant immune cells in the testis and play dual roles in maintaining tissue homeostasis and orchestrating innate immune responses to inflammation. We hypothesise that age-dependent changes in macrophage phenotype and function lead to altered homeostasis, impaired organ function, and worsened reparative responses to acute and chronic testicular inflammation. This project aims to uncover age-dependent alterations in macrophage populations and their functional impact on testicular homeostasis and inflammation. We will study macrophage changes between young and aged mice using advanced techniques such as lineage tracing, high-dimensional flow cytometry, scRNA-seq, and CODEX multiplex imaging. We will explore the phenotype, gene expression, and functional modifications of testicular macrophages, including phagocytosis, proliferation, and inflammation under normal and inflammatory conditions. Furthermore, the project seeks to mitigate inflammaging using innovative strategies. Targeting of macrophages via colony stimulating factor-1 receptor inhibition and of monocytes via C-C chemokine receptor type 2 deficiency is expected to provide insights into their differential roles in testicular functions and inflammation. Moreover, we will target immune communication axes involving macrophage-derived MIF and CD74-expressing Leydig cells aims to explore novel therapeutic avenues. In conclusion, this comprehensive project aims to shed light on the complex interplay between ageing, macrophages, and testicular functions. By unravelling these connections, we hope to pave the way for potential interventions to alleviate inflammaging in the testis and associated pathologies.
DFG Programme
Research Units
