TLR-9 activation aggravates concanavalin A-induced hepatitis via promoting accumulation and activation of liver CD4+ NKT cells.
Increasing evidence suggests that TLRs are involved in the pathogenesis of liver diseases; however, the underlying mechanisms remain obscure. In this study, we found that treatment with CpG-oligodeoxynucleotide (ODN) promoted the accumulation and activation of murine hepatic NKT cells. Additional experiments showed that CpG-ODN preferred to act on CD4(+) NKT cells, while having less effect on CD4(-) NKT cells. The effect of CpG-ODN on liver NKT cells depended on the presence of Kupffer cells and IL-12. Meanwhile, CpG-ODN pretreatment aggravated liver injury and promoted the production of inflammatory cytokines in a Con A-induced fulminant hepatitis model via TLR9 activation. Collectively, our data demonstrate that TLR9 stimulation prefers to promote the accumulation and activation of hepatic CD4(+) NKT cells and suggest that TLR9 signaling might be involved in the pathogenesis of human hepatitis.
Jiang
Wei
W
Institute of Immunology, Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, China.
Sun
Rui
R
Zhou
Rongbin
R
Wei
Haiming
H
Tian
Zhigang
Z
D000208:Acute Disease; D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000276:immunology*; D003208:Concanavalin A / Q000633:toxicity*; D018899:CpG Islands / Q000276:immunology; D006520:Hepatitis, Animal / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D007728:Kupffer Cells / Q000276:immunology / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000473:pathology; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage; D015398:Signal Transduction / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D008024:Ligands; D009838:Oligodeoxyribonucleotides; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D003208:Concanavalin A