Galectin-9 ameliorates immune complex-induced arthritis by regulating FcγR expression on macrophages

Galectin-9 up-regulated FcγRIIb expression of mouse peritoneal macrophages in vitro but down-regulated FcγRIII expression. Galectin-9-treated macrophages stimulated with immune complexes (IC) produced less TNFα and IL-1β but more IL-10 than PBS-treated macrophages. Macrophage enhancing effects on IC-induced C5a and neutrophil chemotactic activity were also diminished for galectin-9-treated macrophages. In galectin-9-treated mice, the severity of IC-induced arthritis was reduced, as were pro-inflammatory cytokine levels in inflamed joints and serum C5a. FcγRIIb expression of macrophages from galectin-9-treated mice was up-regulated, whereas FcγRIII expression was down-regulated. Macrophages from galectin-9-treated mice produced less TNFα and IL-1β but more IL-10 than PBS-treated mice. Disease severity of galectin-9-transgenic mice was milder than wild-type mice, whereas that of galectin-9-deficient mice was exaggerated. Furthermore, macrophage FcγRIIb expression in galectin-9-deficient mice was down-regulated, while FcγRIII expression was up-regulated. These results suggest that galectin-9 suppresses IC-induced inflammation partly by regulating FcγR expression on macrophages.