Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist gegebenenfalls nur via VPN oder Shibboleth (DFN-AAI) möglich.
mehr Informationen...
Different subsets and/or polarized phenotypes of monocytes and macrophages may play distinct roles during the development and resolution of inflammation. Here, we demonstrate in a murine model of rheumatoid arthritis that nonclassical Ly6C− monocytes are required for the initiation and progression of sterile joint inflammation. Moreover, nonclassical Ly6C− monocytes differentiate into inflammatory macrophages (M1), which drive disease pathogenesis and display plasticity during the resolution phase. During the development of arthritis, these cells polarize toward an alternatively activated phenotype (M2), promoting the resolution of joint inflammation. The influx of Ly6C− monocytes and their subsequent classical and then alternative activation occurs without changes in synovial tissue-resident macrophages, which express markers of M2 polarization throughout the course of the arthritis and attenuate joint inflammation during the initiation phase. These data suggest that circulating Ly6C− monocytes recruited to the joint upon injury orchestrate the development and resolution of autoimmune joint inflammation.
[Display omitted]
•Ly6C−, but not Ly6C+, monocytes are crucial for initiation of arthritis•Ly6C− monocytes give rise to inflammatory macrophages during arthritis•Tissue-resident synovial macrophages limit development of arthritis•Recruited macrophages change phenotype from M1 to M2 in situ
Classical Ly6C+ monocytes have been identified as important players in various inflammatory conditions; however, little is known about the role of the nonclassical Ly6C− monocytes. Here, Misharin et al. report that nonclassical Ly6C− monocytes are crucial for the initiation of joint inflammation in a mouse model of rheumatoid arthritis. This study also unveils phenotypical and ontological heterogeneity of the synovial macrophages in steady state and arthritis and reveals how macrophage polarization controls progression and resolution of the disease.