Locally renewing resident synovial macrophages provide a protective barrier for the joint

Culemann S, Grüneboom A, Nicolás-Ávila JÁ, Weidner D, Lämmle KF, Rothe T, Quintana JA, Kirchner P, Krljanac B, Eberhardt M, Ferrazzi F, Kretzschmar E, Schicht M, Fischer K, Gelse K, Faas M, Pfeifle R, Ackermann JA, Pachowsky M, Renner N, Simon D, Haseloff RF, Ekici AB, Bäuerle T, Blasig IE, Vera J, Vöhringer D, Kleyer A, Paulsen F, Schett G, Hidalgo A, Krönke G (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Nature Nature Research

DOI: 10.1038/s41586-019-1471-1

Abstract

Macrophages are considered to contribute to chronic inflammatory diseases such as rheumatoid arthritis1. However, both the exact origin and the role of macrophages in inflammatory joint disease remain unclear. Here we use fate-mapping approaches in conjunction with three-dimensional light-sheet fluorescence microscopy and single-cell RNA sequencing to perform a comprehensive spatiotemporal analysis of the composition, origin and differentiation of subsets of macrophages within healthy and inflamed joints, and study the roles of these macrophages during arthritis. We find that dynamic membrane-like structures, consisting of a distinct population of CX3CR1+ tissue-resident macrophages, form an internal immunological barrier at the synovial lining and physically seclude the joint. These barrier-forming macrophages display features that are otherwise typical of epithelial cells, and maintain their numbers through a pool of locally proliferating CX3CR1− mononuclear cells that are embedded into the synovial tissue. Unlike recruited monocyte-derived macrophages, which actively contribute to joint inflammation, these epithelial-like CX3CR1+ lining macrophages restrict the inflammatory reaction by providing a tight-junction-mediated shield for intra-articular structures. Our data reveal an unexpected functional diversification among synovial macrophages and have important implications for the general role of macrophages in health and disease.

Authors with CRIS profile

Stephan Culemann Lehrstuhl für Genetik Tobias Rothe Department of Medicine 3 – Rheumatology and Immunology Martin Eberhardt Department of Dermatology Fulvia Ferrazzi Institute of Human Genetics Elke Kretzschmar Lehrstuhl für Funktionelle und Klinische Anatomie Martin Schicht Lehrstuhl für Funktionelle und Klinische Anatomie Maria Faas Professur für Immunologie René Pfeifle Department of Medicine 3 – Rheumatology and Immunology Milena Pachowsky Unfallchirurgische Abteilung in der Chirurgischen Klinik Nina Renner Professur für Unfallchirurgie David Simon Department of Medicine 3 – Rheumatology and Immunology Arif Bülent Ekici Institute of Human Genetics Tobias Bäuerle Professur für Multimodale Bildgebung in der präklinischen Forschung Julio Vera González Professur für Tumorimmunologie (Schwerpunkt Systembiologie) David Vöhringer Department of Infection Biology Arnd Kleyer Department of Medicine 3 – Rheumatology and Immunology Friedrich Paulsen Lehrstuhl für Funktionelle und Klinische Anatomie Georg Schett Lehrstuhl für Innere Medizin III Gerhard Krönke Professur für Translationale Immunologie

Additional Organisation(s)

Interdisziplinäres Zentrum für Klinische Forschung

Involved external institutions

Spanish National Center for Cardiovascular Research / Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) ES Spain (ES) Leibniz-Forschungsinstitut für Molekulare Pharmakologie im Forschungsverbund Berlin e.V. (FMP) DE Germany (DE)

How to cite

APA:

Culemann, S., Grüneboom, A., Nicolás-Ávila, J.Á., Weidner, D., Lämmle, K.F., Rothe, T.,... Krönke, G. (2019). Locally renewing resident synovial macrophages provide a protective barrier for the joint. Nature. https://dx.doi.org/10.1038/s41586-019-1471-1

MLA:

Culemann, Stephan, et al. "Locally renewing resident synovial macrophages provide a protective barrier for the joint." Nature (2019).

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