Abstract
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 tissueresident 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.
Original language | English (US) |
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Pages (from-to) | 591-604 |
Number of pages | 14 |
Journal | Cell reports |
Volume | 9 |
Issue number | 2 |
DOIs | |
State | Published - 2014 |
Funding
Northwestern University Cell Imaging Facility and Flow Cytometry Core Facility are supported by NCI Cancer Center Support Grant CA060553 awarded to the Robert H. Lurie Comprehensive Cancer Center. This work was supported by NIH grants AR050250, AR054796, AR064546, AI092490, and HL108795 and funds provided by United States-Israel Binational Science Foundation (2013247), Rheumatology Research Foundation (Agmt 05/06/14), Solovy/Arthritis Research Society, and Arthritis Research UK (grant 18547). We thank Dr. Steffen Jung for providing us with MC-21 antibody. We also thank Drs. Christian Stehlik, Navdeep Chandel, and Richard M. Pope for their critical evaluation of the manuscript and valuable comments.
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology