FcγRIII-expressing macrophages are essential for development of collagen-induced arthritis

IgG-binding Fc receptors, and in particular FcγRIII, are crucial for induction of collagen-induced arthritis (CIA), as FcγRIII-deficient mice are highly protected to arthritis. However, which of the FcγRIII- expressing cells that is responsible for induction of arthritis is not known. In this study, we have addressed this question by purifying different FcγRIII+ cell populations, transferred them to FcγRIII-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 FcγRIII+ CD11b + peritoneal macrophages can render FcγRIII-deficient mice susceptible to CIA. In contrast, FcγRIII- peritoneal macrophages or FcγRIII+ spleenocytes, bone marrow cells, mast cells or monocytes could not mediate this effect. To further evaluate the contribution of the FcγRIII+ macrophages in arthritis, we investigated the cytokine profile in these cells during CIA. The arthritic macrophages exhibited significantly higher mRNA levels of TNFα and IL-12p35 compared with macrophages from normal mice. We conclude that FcγRIII-expressing macrophages, producing pro-inflammatory cytokine and T helper type 1 differentiating factor, are the major effector cells in the induction of CIA.