HMGB1-Promoted and TLR2/4-Dependent NK Cell Maturation and Activation Take Part in Rotavirus-Induced Murine Biliary Atresia

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Biliary atresia (BA) is the most common precipitating factor for liver transplantation in infants. BA is caused by the obstruction of hepatic bile ducts, leading to progressive obstructive jaundice and liver fibrosis. A well-recognized theory is that rotavirus injures biliary epithelia in a mouse model of BA, followed by attack of immunocytes, such as NK cells. We performed this research to investigate whether maturation and activation of NK cells take part in the development of BA. We identified that rotavirus induced HMGB1 release from injured bile ducts. HMGB1 induced NK cell activation in an age-dependent fashion via HMGB1-TLRs-MAPK signaling pathways. Newborn NK cells were unable to eliminate rotavirus-infected cholangiocytes, which caused persistent biliary infection; maturated NK cells were activated gradually and caused persistent biliary injury, which finally led to BA. We identify HMGB1 as an important pro-inflammatory initiator and a critical inducer for maturation of NK cells in the development of BA. HMGB1-induced activation of NK cells may, in part, plays crucial roles in the development of murine BA. Novel therapies targeting HMGB1 or TLRs in patients with BA may be applied in the future to decrease the activity of NK cells in order to inhibit the progression of BA.

Vyšlo v časopise: HMGB1-Promoted and TLR2/4-Dependent NK Cell Maturation and Activation Take Part in Rotavirus-Induced Murine Biliary Atresia. PLoS Pathog 10(3): e32767. doi:10.1371/journal.ppat.1004011
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004011

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