Nonclassical Ly6C(-) monocytes drive the development of inflammatory arthritis in mice.
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.
Division of Rheumatology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Alexander V
AV
Misharin
Division of Rheumatology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Carla M
CM
Cuda
Division of Rheumatology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Rana
R
Saber
Rheumatology Research Group, College of Medical and Dental Sciences, The University of Birmingham, Birmingham B15 2TT, UK.
Jason D
JD
Turner
Division of Rheumatology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Angelica K
AK
Gierut
Department of Pathology, Yale University, School of Medicine, New Haven, CT 06520, USA.
G Kenneth
GK
Haines
Division of Allergy and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Sergejs
S
Berdnikovs
Rheumatology Research Group, College of Medical and Dental Sciences, The University of Birmingham, Birmingham B15 2TT, UK.
Andrew
A
Filer
Rheumatology Research Group, College of Medical and Dental Sciences, The University of Birmingham, Birmingham B15 2TT, UK.
Andrew R
AR
Clark
Rheumatology Research Group, College of Medical and Dental Sciences, The University of Birmingham, Birmingham B15 2TT, UK.
Christopher D
CD
Buckley
Section of Pulmonary and Critical Care, Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
Gökhan M
GM
Mutlu
Division of Pulmonary and Critical Care, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
G R Scott
GR
Budinger
Division of Rheumatology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. Electronic address: h-perlman@northwestern.edu.
Harris
H
Perlman
D000818:Animals; D000950:Antigens, Ly / Q000235:genetics / Q000378:metabolism*; D001169:Arthritis, Experimental / Q000276:immunology* / Q000378:metabolism; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D010641:Phenotype
D000950:Antigens, Ly; C494192:Ly-6C antigen, mouse