Gut commensal bacterial maintain liver innate tolerance for liver regeneration
摘要：
Backgroud:It has been proposed that products of conmmensal bacteria,such as lipopolysaccharide may play a role in repair of liver hepatocytes after partial(67%)hepateetomy.How commensal bacteria affect the ability of liver regeneration remains elusive.Aim:1.To investigate whether commensal bacteria influence the ability of liver regeneration2.To elusidate the potential mechanism of how commensal bacteria affect liver regeneration Methods:In this study,mice were subjected to a 4 week oral administration of antibiotic combination(A/V/N/M)before subjecting to 70%PHx.At different time point of PHx,liver tissues were collected,weighed.A portion of liver were fixed for PCNA,BrdU/IHC,the remnant liver were weighed and liver lymphocy tes were isolated for FACS.Results:we showed that liver regeneration was impaired in antibiotic water-treated mice.Using various antibiotic treatments,we found that ampicillin-sensitive class of commensal bacteria was response for the impaired liver regeneration.The number and activation of NKT cells were up-regulated in the hepatectomized mice by antibiotic water treatment.Deplete or blockade of CD1d-dependent NKT cells could accelerate the regeneration of hepatocytes.Injection of lipopolysaccharide to induce the tolerance of Kupffer cells could partly promote liver regeneration by reducing the number and activation of NKT cells.Conclusion:Our study reveal the importance of commensal bacteria controling hepatocytes repair by negatively regulating hepatic NKT cells via producing lipopolysaccharide to induce the tolerate of Kupffer cells.
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