Novel Insights into the Ontogenetic and Functional Heterogeneity of Macrophages in Synovial Tissue and Bone

Abstract

Inflammatory joint diseases like rheumatoid arthritis (RA) belong to the most prevalent autoimmune disorders. RA is characterized by a massive infiltration of immune cells into synovial tissue, cartilage destruction and bone erosion. The perpetuating inflammatory and destructive milieu is associated with severe pain and culminates in complete disability of synovial joints. The events initiating RA are still not fully understood and the treatments are mainly confined to strategies that modify and inhibit the body’s immune system. Macrophages and osteoclasts (OC) are myeloid cells of the innate immune system and are considered to play a central role in the inflammatory and destructive events of arthritis by production of inflammatory cytokines and mediating pathological bone resorption. In recent years, the use of novel fate mapping strategies identifying the origin and cellular development (ontogeny) of OC and macrophages in conjunction with new genetically modified mouse models, single cell analysis and advanced imaging techniques substantially changed our understanding on the ontogenetic and functional heterogeneity of these cells.

Zusammenfassung

Entzündliche Gelenkerkrankungen wie rheumatoide Arthritis (RA) gehören zu den häufigsten Autoimmunerkrankungen. RA ist durch eine massive Infiltration von Immunzellen in das Synovialgewebe, Knorpelzerstörung und Knochenerosion charakterisiert. Ein andauerndes entzündliches und destruktives Milieu geht mit starken Schmerzen einher und endet schließlich mit vollständigem Funktionsverlust der Gelenke. Die initialen Ereignisse der RA sind immer noch nicht vollständig verstanden und Behandlungen beschränken sich weitestgehend auf Strategien, welche das körpereigene Immunsystem hemmen. Makrophagen und Osteoklasten sind myeloide Zellen, die zum angeborenen Immunsystem gehören. Durch die Produktion von entzündungsfördernden Zytokinen und krankhafter Knochenresorption wird ihnen eine zentrale Rolle bei den entzündlichen und destruktiven Mechanismen der Arthritis zugeschrieben. Mithilfe neuester fate mapping-Strategien, welche den Ursprung und die zelluläre Entwicklung (Ontogenese) von Makrophagen und Osteoklasten identifizierten, sowie innovativer genetisch-modifizierter Mausmodelle, Einzelzell-Analysen und fortschrittlicher Bildgebungstechnik wurde unser Verständnis über die ontogenetische und funktionelle Heterogenität in den vergangenen Jahren substantiell erweitert.

Publication History

Received: 26 July 2021

Accepted: 20 September 2021

Article published online:
18 November 2021

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