Spatiotemporal molecular profiling of macrophage-fibroblast crosstalk defines checkpoints orchestrating onset and resolution of inflammation

Weishaupt K, Chambers D, Dzamukova M, Androšević I, Auger JP, Hueser D, Trzebanski S, Ramming A, Grüneboom A, Schett G, Jung S, Hoffmann MH, Krönke G (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Cell Reports Elsevier (Cell Press)

Book Volume: 45

Article Number: 117091

Journal Issue: 3

DOI: 10.1016/j.celrep.2026.117091

Abstract

SummaryThe molecular details of macrophage-fibroblast crosstalk during the onset and resolution of inflammatory disease remain incompletely understood. Here, we apply a bioinformatic modeling approach based on single-cell RNA sequencing and single-cell assay for transposase-accessible chromatin using sequencing to map heterocellular signaling circuits of synovial macrophage and synovial fibroblast (SF) subsets during various stages of inflammatory arthritis. While SFs function as key pacemakers of synovial inflammation, individual subsets of synovial macrophages support both the perpetuation and the resolution of arthritis. Pro-inflammatory Il1b+ macrophages dominate the early stages of inflammation and retain a substantial intrinsic plasticity that is characterized by chromatin remodeling and an eventual differentiation into Spp1+ macrophages. These cells display a terminally differentiated phenotype, suppress the activation of pro-inflammatory SFs, and initiate the resolution of arthritis by secretion of regulatory mediators, including osteopontin. Our data highlight the dichotomous character of macrophage-fibroblast crosstalk and define the cellular and molecular checkpoints that control the onset and resolution of immune-mediated inflammatory diseases.

Authors with CRIS profile

Katharina Weishaupt Department of Medicine 3 – Rheumatology and Immunology David Chambers Department of Medicine 3 – Rheumatology and Immunology Andreas Ramming Department of Medicine 3 – Rheumatology and Immunology Georg Schett Lehrstuhl für Innere Medizin III Gerhard Krönke Department of Medicine 3 – Rheumatology and Immunology

Involved external institutions

Charité - Universitätsmedizin Berlin DE Germany (DE) Universität zu Lübeck DE Germany (DE) Leibniz-Institut für Analytische Wissenschaften / Leibniz Institute for Analytical Sciences (ISAS) DE Germany (DE) Weizmann Institute of Science IL Israel (IL)

How to cite

APA:

Weishaupt, K., Chambers, D., Dzamukova, M., Androšević, I., Auger, J.P., Hueser, D.,... Krönke, G. (2026). Spatiotemporal molecular profiling of macrophage-fibroblast crosstalk defines checkpoints orchestrating onset and resolution of inflammation. Cell Reports, 45(3). https://doi.org/10.1016/j.celrep.2026.117091

MLA:

Weishaupt, Katharina, et al. "Spatiotemporal molecular profiling of macrophage-fibroblast crosstalk defines checkpoints orchestrating onset and resolution of inflammation." Cell Reports 45.3 (2026).

BibTeX: Download