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Cell Rep. 2014 Oct 23;9(2):591-604. doi: 10.1016/j.celrep.2014.09.032. Epub 2014 Oct 16.

Nonclassical Ly6C(-) monocytes drive the development of inflammatory arthritis in mice.

Author information

1
Division of Rheumatology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
2
Rheumatology Research Group, College of Medical and Dental Sciences, The University of Birmingham, Birmingham B15 2TT, UK.
3
Department of Pathology, Yale University, School of Medicine, New Haven, CT 06520, USA.
4
Division of Allergy and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
5
Section of Pulmonary and Critical Care, Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
6
Division of Pulmonary and Critical Care, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
7
Division of Rheumatology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. Electronic address: h-perlman@northwestern.edu.

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 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.

PMID:
25373902
PMCID:
PMC4223808
DOI:
10.1016/j.celrep.2014.09.032
[Indexed for MEDLINE]
Free PMC Article

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