Mycophenolic acid upregulates B7-DC expression on dendritic cells, which is associated with impaired allostimulatory capacity of dendritic cells.
In addition to its effects on lymphocytes, mycophenolic acid (MPA) may inhibit the allostimulatory capacity of dendritic cells (DC) via unknown mechanisms. B7-H1 and B7-DC surface markers on DC negatively regulate T-cell responses via the receptor PD-1. In this study, we sought to investigate whether B7-H1 and B7-DC are responsible for the inhibitory functions of MPA on DC. Mouse bone marrow-derived DC were cultured with recombinant granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4 in the presence or absence of MPA (0.01 micromol and 0.1 micromol). The DC phenotype was assessed by flow cytometry, their immunostimulatory capacity measured by mixed lymphocyte reaction (MLR), and cytokine production by ELISA. The results showed that MPA not only inhibited the expression of major histocompatibility complex (MHC) class II and costimulatory molecules CD80 and CD86 but upregulated B7-DC expression on mature DC induced by LPS. These findings were associated with a reduced allostimulatory ability and an altered cytokine secretion pattern of DC. Thus, we suggest that MPA upregulates B7-DC expression during DC maturation induced by LPS in vitro, an effect that may be responsible for MPA-mediated inhibitory effects on the allostimulatory capacity of DC.
Geng
L
L
Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Jiang
G
G
Xie
H
H
Fang
Y
Y
Dong
S
S
Chen
Y
Y
Shen
M
M
Zheng
S
S
D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D018122:B7-1 Antigen / Q000235:genetics*; D016923:Cell Death; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009173:Mycophenolic Acid / Q000494:pharmacology*; D014184:Transplantation, Homologous
D015703:Antigens, CD; D018122:B7-1 Antigen; D016207:Cytokines; D008070:Lipopolysaccharides; D009173:Mycophenolic Acid