DFG Collaborative Research Centre / Transregio 412

Internal area
B02 Area B — Inflammation & fibrosis

Understanding and modulating hepatic macrophage functionality in MASLD

Graphical abstract of project B02
Graphical abstract: macrophage states from healthy liver to fibrosis.

Summary

Liver macrophages are central in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD). We will characterize the phenotypic, spatial and functional heterogeneity of macrophages including cell-cell interactions and identify targetable ligand-receptor pairs.

Our findings will provide a comprehensive picture of how hepatic macrophage subsets contribute to altered metabolism, inflammation and fibrosis in MASLD and opportunities for novel therapeutic strategies.

“Macrophages are not simply bystanders in MASLD — they decide whether the liver resolves injury or progresses towards fibrosis.”

Frank Tacke, Principal investigator B02

Research objectives

  1. Characterize the phenotypic and spatial heterogeneity of hepatic macrophages in human MASLD.
  2. Identify targetable ligand–receptor pairs between macrophages, hepatocytes and stellate cells.
  3. Test functional modulation of candidate pathways in mouse models and liver-on-a-chip systems.

Key methods

  • Single-cell RNA sequencing of human liver biopsies
  • Spatial transcriptomics and multiplex imaging
  • Macrophage–hepatocyte co-culture on liver-on-a-chip

Project video

How macrophages shape MASLD — B02 in 3 minutes

Selected publications

Macrophage heterogeneity in MASLD: from single-cell atlases to therapeutic targeting

Journal of Hepatology · 2026 · DOI

Spatial transcriptomics reveals zonated macrophage niches in human MASH

Nature Metabolism · 2025 · DOI

EASL–EASD–EASO clinical practice guidelines on the management of MASLD

Journal of Hepatology · 2024 · DOI

All B02 publications