Galectin-9 ameliorates immune complex-induced arthritis by regulating Fc gamma R expression on macrophages.
Galectin-9 up-regulated Fc gamma RIIb expression of mouse peritoneal macrophages in vitro but down-regulated Fc gamma RIII expression. Galectin-9-treated macrophages stimulated with immune complexes (IC) produced less TNFalpha and IL-1 beta 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. Fc gamma RIIb expression of macrophages from galectin-9-treated mice was up-regulated, whereas Fc gamma RIII expression was down-regulated. Macrophages from galectin-9-treated mice produced less TNFalpha and IL-1 beta 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 Fc gamma RIIb expression in galectin-9-deficient mice was down-regulated, while Fc gamma RIII expression was up-regulated. These results suggest that galectin-9 suppresses IC-induced inflammation partly by regulating Fc gamma R expression on macrophages.
Department of Immunology and Immunopathology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
Tomohiro
T
Arikawa
Kota
K
Watanabe
Masako
M
Seki
Akihiro
A
Matsukawa
Souichi
S
Oomizu
Ken-mei
KM
Sakata
Atsuko
A
Sakata
Masaki
M
Ueno
Naoki
N
Saita
Toshiro
T
Niki
Akira
A
Yamauchi
Mitsuomi
M
Hirashima
D000818:Animals; D000936:Antigen-Antibody Complex / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D005434:Flow Cytometry; D037161:Galectins / Q000276:immunology*; D006651:Histocytochemistry; D017737:Macrophages, Peritoneal / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D017452:Receptors, IgG / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013047:Specific Pathogen-Free Organisms; D018709:Statistics, Nonparametric
D000936:Antigen-Antibody Complex; D016207:Cytokines; C080571:Fc gamma receptor IIB; D037161:Galectins; D012333:RNA, Messenger; D017452:Receptors, IgG; C508186:galectin 9, mouse