Liver Regeneration after Partial Hepatectomy Is Not Impaired in Mice with Double Deficiency of Myd88 and IFNAR Genes

Abstract

Liver regeneration is known to occur in mice lacking one or more Toll-like receptors (TLRs) or the adaptor protein MyD88. Though MyD88 is required for signaling by many TLRs, others signal via MyD88-independent pathways, leading to the induction of type I interferons (IFNs). Here, we assessed liver regeneration after partial hepatectomy (PH) in mice lacking both MyD88 and the type I IFN receptor (Myd88-IFNAR double-KO). Approximately 28% of Myd88-IFNAR double-KO mice had gross liver lesions prior to surgery. In mice without lesions, Myd88-IFNAR deficiency abrogated the increase in circulating IL-6 after PH but did not impair hepatocyte BrdU incorporation, mitotic figure counts, or recovery of liver-to-body weight ratios. These results indicate that type I IFNs are not responsible for the preservation of liver regeneration in Myd88-deficient mice, and they also cast doubt on the idea of microbial products being essential triggers of liver regeneration in mice undergoing PH.