Andrén M, Xiang Z, Nilsson G, Kleinau S
Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden.
Scand J Immunol. 2006 Apr;63(4):282-9. doi: 10.1111/j.1365-3083.2006.01743.x.
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.
IgG结合性Fc受体，尤其是FcγRIII，对于胶原诱导的关节炎（CIA）的诱导至关重要，因为FcγRIII缺陷型小鼠对关节炎具有高度抵抗力。然而，尚不清楚哪种表达FcγRIII的细胞负责诱导关节炎。在本研究中，我们通过纯化不同的FcγRIII(+)细胞群体，将它们转移到FcγRIII缺陷型小鼠中，并研究受体小鼠是否会发生关节炎，从而解决了这个问题。细胞群体从脾脏、骨髓和腹腔中分离出来。我们的结果表明，FcγRIII(+) CD11b(+)腹腔巨噬细胞可使FcγRIII缺陷型小鼠易患CIA。相比之下，FcγRIII(-)腹腔巨噬细胞或FcγRIII(+)脾细胞、骨髓细胞、肥大细胞或单核细胞不能介导这种效应。为了进一步评估FcγRIII(+)巨噬细胞在关节炎中的作用，我们研究了CIA期间这些细胞中的细胞因子谱。与正常小鼠的巨噬细胞相比，关节炎巨噬细胞中TNFα和IL-12p35的mRNA水平显著更高。我们得出结论，表达FcγRIII的巨噬细胞，产生促炎细胞因子和1型辅助性T细胞分化因子，是诱导CIA的主要效应细胞。
