FcgammaRIII-expressing macrophages are essential for development of collagen-induced arthritis.
IgG-binding Fc receptors, and in particular FcgammaRIII, are crucial for induction of collagen-induced arthritis (CIA), as FcgammaRIII-deficient mice are highly protected to arthritis. However, which of the FcgammaRIII-expressing cells that is responsible for induction of arthritis is not known. In this study, we have addressed this question by purifying different FcgammaRIII(+) cell populations, transferred them to FcgammaRIII-deficient mice and studied if the recipient mice can develop arthritis. The cell populations were isolated from spleen, bone marrow and the peritoneal cavity. Our results show that FcgammaRIII(+) CD11b(+) peritoneal macrophages can render FcgammaRIII-deficient mice susceptible to CIA. In contrast, FcgammaRIII(-) peritoneal macrophages or FcgammaRIII(+) spleenocytes, bone marrow cells, mast cells or monocytes could not mediate this effect. To further evaluate the contribution of the FcgammaRIII(+) macrophages in arthritis, we investigated the cytokine profile in these cells during CIA. The arthritic macrophages exhibited significantly higher mRNA levels of TNFalpha and IL-12p35 compared with macrophages from normal mice. We conclude that FcgammaRIII-expressing macrophages, producing pro-inflammatory cytokine and T helper type 1 differentiating factor, are the major effector cells in the induction of CIA.
Andrén
M
M
Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden.
Xiang
Z
Z
Nilsson
G
G
Kleinau
S
S
D000818:Animals; D001169:Arthritis, Experimental / Q000209:etiology / Q000276:immunology* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000502:physiology; D024043:Collagen Type II / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D007074:Immunoglobulin G / Q000096:biosynthesis; D017737:Macrophages, Peritoneal / Q000378:metabolism* / Q000637:transplantation; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000166:cytology / Q000502:physiology
D024043:Collagen Type II; D016207:Cytokines; C485700:Fcgr3 protein, mouse; D007074:Immunoglobulin G; D017452:Receptors, IgG