Interferon-gamma is an autocrine mediator for dendritic cell maturation.
Maturation of dendritic cells (DC) is critical for efficient antigen presentation and initiation of an immune response. Interferon-gamma (IFN-gamma) is an important Th1 cytokine. In this study, we investigated the role of IFN-gamma in DC maturation using either IFN-gamma receptor deficient- or IFN-gamma overexpression-models. We showed that immature DC generated in vitro from bone marrow (BM) progenitor cells produced low level of IFN-gamma. After LPS stimulation, DC produced more IFN-gamma, and IFN-gamma productions were at comparable levels among C57BL/6 mice-derived DC (C57BL/6 DC), wild-type 129 mice-derived DC (129 DC) and IFN-gamma receptor deficient 129 mice-derived DC (IFN-gammaR-/-DC). We found that IFN-gammaR-/-DC exhibited decreased expression of CD54, CD86, reduced capacity to secrete IL-1beta and IL-12p70, and impaired capacity to stimulate alloreactive T cells and to drive Th1 differentiation. Transfection of IFN-gamma gene into DC promoted DC to express higher CD40, CD54, CD80, CD86, CCR7 and I-Ab, secrete more IL-1beta and IL-12p70, and more potently activate both CD4 and CD8 T cells. These data suggest that IFN-gamma signaling pathway is important for the maturation of DC in an autocrine fashion.
Pan
Jianping
J
Institute of Immunology, Zhejiang University, Hangzhou 310031, PR China.
Zhang
Minghui
M
Wang
Jianli
J
Wang
Qingqing
Q
Xia
Dajing
D
Sun
Wenji
W
Zhang
Lihuang
L
Yu
Hai
H
Liu
Yongjun
Y
Cao
Xuetao
X
D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD / Q000096:biosynthesis; D019898:Autocrine Communication; D051940:B7-2 Antigen; D001854:Bone Marrow Cells / Q000187:drug effects; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D018345:Mice, Knockout; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D017471:Receptors, Interferon / Q000235:genetics / Q000502:physiology; D013234:Stem Cells / Q000187:drug effects; D000096743:Interferon gamma Receptor
D015703:Antigens, CD; D051940:B7-2 Antigen; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D019707:Receptors, Chemokine; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor; C497965:Cd86 protein, mouse