TOKITA Daisuke    Department   School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine    Position
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	Endotoxin modulates the capacity of CpG-activated liver myeloid DC to direct Th1-type responses.
Journal	Formal name：European journal of immunology Abbreviation：Eur J Immunol ISSN code：00142980/00142980
Domestic / Foregin	Foregin
Volume, Issue, Page	36(9),pp.2483-93
Author and coauthor	Abe Masanori, Tokita Daisuke, Raimondi Giorgio, Thomson Angus W
Authorship	Lead author
Publication date	2006/09
Summary	DC are believed to play important roles in the induction and regulation of immune responses in the liver, an organ implicated in peripheral tolerance. Since the liver is located downstream of the gut, it is constantly exposed to bacterial LPS. Our recent observations indicate that prior exposure to endotoxin modulates subsequent liver DC responses to this TLR4 ligand. In this study, we demonstrate that endotoxin modifies the capacity of mouse liver myeloid DC (MDC) activated by CpG (TLR9 ligand) to direct Th1-type responses. IL-12 production by liver MDC was significantly lower than that of spleen MDC following CpG or Imiquimod (R837; TLR7 ligand) activation in vitro. In addition, allogeneic T cells stimulated by CpG-activated liver MDC secreted significantly lower levels of IFN-gamma than T cells stimulated with CpG-activated spleen MDC. A similar effect on liver DC was observed in response to in vivo CpG administration. This effect may be explained by exposure of the DC to endotoxin, because LPS attenuated IL-12 production by CpG-stimulated liver MDC, both in vitro and in vivo. Moreover, attenuation of the response to CpG was not observed in liver MDC from TLR4-mutant (C3H/HeJ) mice, in which TLR4 signaling is impaired. These data suggest that endotoxin-induced 'cross-tolerance' to TLR ligands in liver DC may contribute to down-regulation of hepatic immune responses.
DOI	10.1002/eji.200535767
PMID	16917958