Euroasian Journal of Hepato-Gastroenterology

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VOLUME 2 , ISSUE 1 ( January-June, 2012 ) > List of Articles

ORIGINAL ARTICLE

Suppression of Inflammatory Mucosal Milieu by Administration of Regulatory Dendritic Cells in an Animal Model of Primary Biliary Cirrhosis

Morikazu Onji, Mamun Al-Mahtab, Sheikh Mohammad Fazle Akbar, Shiyi Chen, Masanori Abe, Osamu Yoshida, Yoshio Ikeda, Yoichi Hiasa

Citation Information : Onji M, Al-Mahtab M, Mohammad Fazle Akbar S, Chen S, Abe M, Yoshida O, Ikeda Y, Hiasa Y. Suppression of Inflammatory Mucosal Milieu by Administration of Regulatory Dendritic Cells in an Animal Model of Primary Biliary Cirrhosis. Euroasian J Hepatogastroenterol 2012; 2 (1):30-34.

DOI: 10.5005/jp-journals-10018-1028

License: CC BY-NC 4.0

Published Online: 01-01-2012


Abstract

Background/Aim: Primary biliary cirrhosis (PBC) is an autoimmune disease of the liver for which a curative therapy is still lacking. The aim of this preclinical study was to assess if down regulation of host immunity by regulatory dendritic cells (DC) bears therapeutic implications in a murine model of PBC. Methods: An animal model of PBC was established by injecting 5 mg/kg polyinosinic polycytidylic acid (poly I:C) twice a week in female C57BL/6 mice. Regulatory DC were produced by culturing bone marrow DC with interleukin-10 and lipopolysaccharides without or with pyruvate dehydrogenase complex (PDC, 1 μg/ml). Regulatory DC and PDC-pulsed regulatory DC were injected intraperitoneally trice (8, 12 and 20 weeks after starting of poly I:C administration) to PBC model mice. Antimitochondrial antibody (AMA) was checked in the sera and liver histology was assessed to evaluate the effect of regulatory DC on inflammatory hepatic mucosal milieu. Results: AMA in the sera and progressive infiltration of mononuclear cells were detected in all C57BL/6 due to administration of poly I:C. Injection of regulatory DC or PDCpulsed regulatory DC for 3 times caused significant reduction of infiltrating mononuclear cells in 4 of 5 PBC model mice. However, the effect of regulatory DC on AMA negativity was not documented in murine model of PBC. Conclusion: This pilot study inspires optimisms that regulatory DC may be an immune therapeutic approach for treating PBC, however, further study about nature of antigens, dose of antigens, duration of therapy and protocol of administration of regulatory DC need further analyses.


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