Accumulation and Activation of Liver CD4 A-Induced Hepatitis via Promoting TLR-9 Activation Aggravates Concanavalin

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 (cid:1) NKT cells, while having less effect on CD4 (cid:2) 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 (cid:1) NKT cells and suggest that TLR9 signaling might be involved in the pathogenesis of human hepatitis. The Journal of Immunology, 2009, 182: 3768–3774.

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