Fas signal links innate and adaptive immunity by promoting dendritic-cell secretion of CC and CXC chemokines.
Dendritic cells (DCs) and chemokines are important in linking innate and adaptive immunity. We previously reported that Fas ligation induced interleukin 1beta (IL-1beta)-dependent maturation and IL-1beta-independent survival of DCs, with extracellular signal-regulated kinase (ERK) and nuclear factor-kappaB (NF-kappaB) signaling pathways involved, respectively. We describe here that Fas ligation induced DCs to rapidly produce both CXC and CC chemokines, including macrophage inflammatory protein 2 (MIP-2), MIP-1alpha, MIP-1beta, monocyte chemoattractant protein 1 (MCP-1), RANTES (regulated on activation normal T cell expressed and secreted), and TARC (thymus and activation-regulated chemokine), resulting in enhanced chemoattraction of neutrophils and T cells by Fas-ligated DCs in vivo or by its supernatant in vitro. These chemokines work synergistically in chemoattraction of neutrophils and T cells with MIP-2 more important for neutrophils, MIP-1alpha and TARC more important for T cells. Moreover, Fas-ligated DCs increased endocytosis by neutrophils and activation and proliferation of antigen-specific naive T cells. Fas ligation-induced DC secretion of chemokines involves Ras/Raf/mitogen-activated protein kinase kinase (MEK)/ERK activation and is ERK, but not NF-kappaB, dependent. Activation of caspases, including caspase 1, but not IL-1 autocrine action, is involved in this process. These data indicate that Fas signaling provides a key link between innate response and adaptive immunity by promoting DC chemokine production.
Guo
Zhenhong
Z
Institute of Immunology, Second Military Medical University, 800 Xiangyin Rd, Shanghai 200433, People's Republic of China.
Zhang
Minghui
M
Tang
Hua
H
Cao
Xuetao
X
D000818:Animals; D020169:Caspases / Q000378:metabolism; D019742:Chemokines, CC / Q000378:metabolism*; D019743:Chemokines, CXC / Q000378:metabolism*; D002633:Chemotaxis / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007111:Immunity, Cellular; D007113:Immunity, Innate; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D019014:fas Receptor / Q000276:immunology*; D018631:ras Proteins / Q000378:metabolism
D019742:Chemokines, CC; D019743:Chemokines, CXC; C491899:Fas protein, mouse; D018124:Receptors, Tumor Necrosis Factor; D019014:fas Receptor; D048049:Extracellular Signal-Regulated MAP Kinases; D020169:Caspases; D018631:ras Proteins