Differential IL-10 production by DCs determines the distinct adjuvant effects of LPS and PTX in EAE induction.
Pertussis toxin (PTX) is used as an adjuvant to induce EAE in mice as a model of MS. Although LPS and PTX are similar in their ability to mature dendritic cells (DCs) and in their adjuvant properties, here we demonstrate that LPS does not induce EAE development. We also demonstrate that DCs treated with PTX (PTX-DCs) are able to induce EAE, whereas DCs treated with LPS (LPS-DCs) fail to induce EAE. We determine that a key difference between LPS-DCs and PTX-DCs is that LPS-DCs produce larger amounts of IL-10. IL-10(-/-) -DCs treated with LPS promote stronger IFN-γ and IL-17 production and T-cell proliferation than WT DCs treated with LPS in a coculture system. Finally, we demonstrate that EAE can be successfully induced when IL-10(-/-) -DCs treated with LPS are used as an adjuvant, whereas the use of PTX-DCs overexpressing IL-10 as an adjuvant markedly controls EAE development. These results indicate that the inability of LPS to induce EAE is based on the induction of high levels of IL-10 in the targeted DCs, providing insight into the mechanisms responsible for the induction of EAE.
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Haiyan
H
Zhou
Yanming
Y
Wang
Qiaoshi
Q
Lian
Bo
B
Yang
Yonglei
Y
Ma
Xiaodong
X
Wu
Shuhui
S
Sun
Yongjun
Y
Liu
Bing
B
Sun
D000276:Adjuvants, Immunologic / Q000009:adverse effects* / Q000494:pharmacology; D000818:Animals; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D020381:Interleukin-17 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D008070:Lipopolysaccharides / Q000009:adverse effects* / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D037342:Pertussis Toxin / Q000633:toxicity*
D000276:Adjuvants, Immunologic; D020381:Interleukin-17; D008070:Lipopolysaccharides; D016753:Interleukin-10; D007371:Interferon-gamma; D037342:Pertussis Toxin
Dendritic cells; EAE; IL-10; LPS; Pertussis toxin (PTX)