Abstract
Background: Chronic colitis-harboring TCRα− / − × AIM− / − mice showed PBC-like bile duct damage in the liver. Bacterial infection is one of the candidates for the pathogenesis of PBC. We demonstrated that the bacterial cell wall component lipotheicoic acid (LTA) was detected at sites of inflammation around damaged bile ducts in PBC patients. The aim of this study was to investigate the pathophysiology of the liver and other organs in TCRα− / − × AIM− / − mice.Methods: Thirteen female TCRα− / − × AIM− / − mice were sacrificed at 24 weeks of age. The liver, stomach, small intestine, colon, pancreas, kidney and spleen were studied for pathological examination. Using anti-LTA antibody as the primary antibody, an immunohistochemical study was carried out.Results: In the liver, LTA was mainly detected in the portal area with inflammation, and some of the cytoplasm of hepatocytes. Inflammations were also observed in the stomach, intestine, pancreas and kidney. Throughout the gastrointestinal tract, from the stomach to the colon, LTA was detected in the epithelium at sites of inflammation. Furthermore, LTA was detected around both pancreatic ducts with inflammation and distal renal tubules with inflammation.Conclusions: The development of inflammations in the liver as well as extensive organs, strongly suggests a close relationship between bile duct damage and systemic multifocal epithelial inflammations, perhaps involving bacterial LTA, in TCRα− / − × AIM− / − mice.
Highlights
Intrahepatic bile ducts are targets for inflammation in both primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC), yet the mechanisms of biliary epithelial cell damage in these diseases are not clearly understood
We reported that lipotheicoic acid (LTA) was detected at the portal tract in stage 1–2 PBC with chronic non-suppurative destructive cholangitis (CNSDC)
LTA immunoreactivity was detectable in the livers of 5 of 13 (38.4%) TCRa2/2 £ AIM2/2 mice
Summary
Intrahepatic bile ducts are targets for inflammation in both primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC), yet the mechanisms of biliary epithelial cell damage in these diseases are not clearly understood. We previously reported that defects in apoptosis inhibitor expressed by macrophages (AIM) affected portal inflammation as well as biliary epithelial cell damage in the liver in colitisharboring female TCRa-deficient (TCRa2/2 ) mice [1]. The TCRa2/2 mouse is an ulcerative colitis (UC)-like colitis-harboring mouse, the pattern of bile duct damage was closer to PBC in TCRa2/2 £ AIM2/2 double-knockout mice. Chronic colitis-harboring TCRa2/2 £ AIM2/2 mice showed PBC-like bile duct damage in the liver. We demonstrated that the bacterial cell wall component lipotheicoic acid (LTA) was detected at sites of inflammation around damaged bile ducts in PBC patients. The aim of this study was to investigate the pathophysiology of the liver and other organs in TCRa2/2 £ AIM2/2 mice
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