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

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