Molecular Assessment of the Acute Damage-Response in Stromal Resident Tissue Macrophages.

• Applicant: Professor Dr. Stefan Uderhardt
• Subject Area: Immunology ; Rheumatology ; Cell Biology
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 448121523

In my own previous work, I could identify resident tissue macrophages (RTM) as anti-inflammatory protectors of stromal integrity. The underlying molecular mechanisms that drive and regulate this tissue-protective function, however, have not been studied so far, mostly due to technical limitations. Understanding how RTM operate, though, not in isolation but within the actual stroma constitutes an indispensable prerequisite for targeting macrophages therapeutically in inflammatory diseases and has far-reaching, cross-disciplinary implications, for instance in cancer immunology or vaccinology. Recent technological advances allowed me to directly and comprehensively study RTM within their natural tissue microenvironment with high level of detail. In my grant proposal, I propose an exploratory tissue biology approach, aiming to assess molecular and cellular determinants of RTM activation in situ on multiple levels, integrating tissue-level imaging data as well as transcriptional cell profiling. Specifically, I propose the extensive characterization of the spatiotemporal dynamics of key inflammatory signaling pathways and their functional implications in interstitial RTM activation upon different challenges within their own tissue environment. Further, I seek to assess early transcriptional damage responses in RTM and other stromal cells in order to identify novel targets, not only to treat inflammatory diseases but actually prevent them on the level of tissue homeostasis.

• DFG Programme: Research Grants