Augmentation of antigen-presenting and Th1-promoting functions of dendritic cells by WSX-1(IL-27R) deficiency.
WSX-1 is the alpha subunit of the IL-27R complex expressed by T, B, NK/NKT cells, as well as macrophages and dendritic cells (DCs). Although it has been shown that IL-27 has both stimulatory and inhibitory effects on T cells, little is known on the role of IL-27/WSX-1 on DCs. LPS stimulation of splenic DCs in vivo resulted in prolonged CD80/CD86 expression on WSX-1-deficient DCs over wild-type DCs. Upon LPS stimulation in vitro, WSX-1-deficient DCs expressed Th1-promoting molecules higher than wild-type DCs. In an allogeneic MLR assay, WSX-1-deficient DCs were more potent than wild-type DCs in the induction of proliferation of and IFN-gamma production by responder cell proliferation. When cocultured with purified NK cells, WSX-1-deficient DCs induced higher IFN-gamma production and killing activity of NK cells than wild-type DCs. As such, Ag-pulsed WSX-1-deficient DCs induced Th1-biased strong immune responses over wild-type DCs when transferred in vivo. WSX-1-deficient DCs were hyperreactive to LPS stimulation as compared with wild-type DCs by cytokine production. IL-27 suppressed LPS-induced CD80/86 expression and cytokine production by DCs in vitro. Thus, our study demonstrated that IL-27/WSX-1 signaling potently down-regulates APC function and Th1-promoting function of DCs to modulate overall immune responses.
Wang
Sen
S
Department of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga, Japan.
Miyazaki
Yoshiyuki
Y
Shinozaki
Yukari
Y
Yoshida
Hiroki
H
D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology; D051940:B7-2 Antigen / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D018121:Receptors, Cytokine / Q000172:deficiency / Q000276:immunology*; D018123:Receptors, Interleukin; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*
D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; C484747:Il27ra protein, mouse; D008070:Lipopolysaccharides; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; D007371:Interferon-gamma