Lipoteichoic acid may affect the pathogenesis of PBC-like bile duct damage and might be involved in systemic multifocal epithelial inflammations in chronic colitis-harboring TCRα^−/−×AIM^−/− mice

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.

• TCRα^{− / −} mice
• LTA
• primary biliary cirrhosis
• primary sclerosing cholangitis
• multiple organ dysfunction syndrome (MODS)

Acknowledgements

We thank Dr Miyazaki (Center for Immunology, University of Texas Southwestern Medical Center) for the kind gift of TCRα^{− / −} × AIM^{− / −} mice. This study is partly supported by Health and Labour Sciences Research Grants (from the Ministry of Health, Labour and Welfare of Japan) for the Research on Measures for Intractable Diseases, and Dr Yayoi Yoshioka Foundation (Tokyo, Japan). We also thank Ms. Sakayori, Mr Takeiri, and Mr Karita for their skillful technical assistance.