Identifying signatures of chronic inflammation in human lymph node mononuclear phagocytes

• Applicant: Jake Thomas, Ph.D.
• Subject Area: Immunology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 521441776

Lymph nodes form a physical network across the body, acting as the primary sites for the initiation of adaptive immune responses. Human lymph nodes can exhibit extended periods of pathological chronic inflammation, which result in pain, fibrosis and tissue dysfunction. Mononuclear phagocytes (MNPs), which include macrophages, monocytes and dendritic cells, act as critical regulators of the initiation, maintenance and termination of immune responses. Lymph node MNPs are therefore predicted to have key roles in regulating chronic inflammatory events, but little is known about how resident MNPs are perturbed specifically during chronic inflammation.To address this shortcoming, the central aim of the proposal is to elucidate the unique transcriptional, phenotypic, spatial and functional characteristics of MNPs during chronic inflammation in human lymph nodes. This will be enabled through the comparison of MNPs derived from a cohort of healthy, acutely inflamed and chronically inflamed human lymph node samples. These comparisons will be accomplished using cutting-edge experimental approaches, including single cell mRNA sequencing, flow cytometry, multiplexed imaging and 3D in vitro culture models. This will, for the first time, allow the comprehensive mapping and characterization of emergent MNP properties during chronic inflammation. As chronic inflammation is a defining characteristic of many pathologies, this proposal will serve as a foundation for future research, permitting the identification of unique MNP states in other disease contexts, such as cancer.

• DFG Programme: WBP Position