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Recent evidence suggests that hepatic dendritic cells (HDCs) contribute to the evolution of chronic liver diseases. However, the HDC subsets involved and the mechanisms driving these responses are still poorly understood. In this study, we have investigated the role of the fractalkine receptor CX 3 CR1 in modulating monocyte-derived dendritic cell (moDC) differentiation during liver inflammation. The phenotype of HDC and functional relevance of CX 3 CR1 was assessed in mice following necro-inflammatory liver injury induced by the hepatotoxic agent carbon tetrachloride (CCl 4 ) and in steatohepatitis caused by a methionine/choline-deficient (MCD) diet. In both the experimental models, hepatic inflammation was associated with a massive expansion of CD11c + /MHCII high /CD11b + myeloid HDCs. These cells also expressed the monocyte markers Ly6C, chemokine (C-C Motif) receptor 2 (CCR2), F4/80 and CD88, along with CX 3 CR1, allowing their tentative identification as moDCs. Mice defective in CX 3 CR1 showed a reduction in liver-moDC recruitment following CCl 4 poisoning in parallel with a defective maturation of monocytes into moDCs. The lack of CX 3 CR1 also affected moDC differentiation from bone marrow myeloid cells induced by granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4) in vitro. In wild-type mice, treatment with the CX 3 CR1 antagonist CX3-AT (150 µg, i.p.) 24 h after CCl 4 administration reduced liver moDC S and significantly ameliorated hepatic injury and inflammation. Altogether, these results highlight the possible involvement of moDCs in promoting hepatic inflammation following liver injury and indicated a novel role of CX 3 CL1/CX 3 CR1 dyad in driving the differentiation of hepatic moDCs.

Neuroinflammation plays a role in cancer chemotherapy-induced chronic pain. Thus far, most studies have focused on neuroinflammation suppression. However, there are limited reports of which factor is involved in the transition from acute inflammation to chronic inflammation, resulting in neuroinflammation and chronic pain. Here, we compared the inflammatory reaction and pain response induced by LPS and paclitaxel. LPS (0.5 mg/kg) or paclitaxel (2 mg/kg/day for 5 days) was administered intraperitoneally to mice, and mechanical allodynia was examined by von Frey test. LPS induced transient mechanical allodynia, whereas paclitaxel induced persistent mechanical allodynia. The CD86/CX3CR1 ratio remained unchanged due to CX3CR1 elevation following LPS injection, whereas the ratio was increased on day 1 after paclitaxel injection. LPS also increased CD45, CCL2, and CCL5 mRNA in the spinal cord and circulating pro- and anti-inflammatory cytokines 1 day after injection; however, the pattern was not consistent. Paclitaxel gradually increased inflammatory cytokines in the spinal cord. CX3CR1 might be involved in blocking the transition from acute pain to persistent pain in the LPS group. In addition, serum IL-4 and IL-10 elevation in the LPS group may be associated with chronic pain prevention. Therefore, targeting CX3CR1, IL-4, and IL-10 might be an alternative therapeutic strategy.