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.
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.
The unfinished business of primary biliary cirrhosis. J Hepatol Sep 2008;49(3):451-60
Managing systemic symptoms in chronic liver disease. J Hepatol 2012;56(Suppl):S46-55
J Hepatol 2009;51:237-67
Ten-year survival in ursodeoxycholic acidtreated patients with primary biliary cirrhosis. The UDCA-PBC Study Group. Hepatology 1999;29:1668-71
Randomised controlled trials of ursodeoxycholic-acid therapy for primary biliary cirrhosis: A meta-analysis. Lancet 1999;354:1053-60
Study group of intractable liver diseases for research on a specific disease, Health Science Research Grant, Ministry of Health, Labour and Welfare of Japan. The efficacy of ursodeoxycholic acid and bezafibrate combination therapy for primary biliary cirrhosis: A prospective, multicenter study. Hepatol Res 2008;38:557-64
Dendritic cells in clinics. Tokyo: Spirnger 2008:155-69
Protective role of interleukin-10-producing regulatory dendritic cells against murine autoimmune gastritis. Gastroenterol 2008;43:100-07
Regulatory dendritic cells pulsed with carbonic anhydrase I protect mice from colitis induced by CD4+CD25-T Cells. J Immunol 1 Mar 2012;188(5):2164-72
Viral infection prevents diabetes by inducing regulatory T cells through NKT cell-plasmacytoid dendritic cell interplay. J Exp Med 2011; 208:729-45
Critical role for TNF in the induction of human antigen-specific regulatory T cells by tolerogenic dendritic cells. J Immunol 2010;185:1412-18
The immunotherapeutic potential of dendritic cells in type 1 diabetes. Clin Exp Immunol. 2010;161:197-207
Treatment of autoimmune arthritis using RNA interferencemodulated dendritic cells. J Immunol 2010;184:6457-64
Dendritic cells modified by vitamin D: Future immunotherapy for autoimmune diseases. Vitam Horm 2011;86:63-82
Dendritic cells as potential targets for mucosal immunotherapy. Curr Opin Allergy Clin Immunol 2009;9:554-57
Early development of primary biliary cirrhosis in female C57BL/6 mice due to poly I: C administration. Liver International 2005;25:595-603
Autoimmune cholangitis in the SJL/J mouse is antigen nonspecific. Dev Immunol 2002;9:103-11
Increased nitric oxide (NO) production by antigen presenting dendritic cells is responsible for low allogenic mixed leukocyte reaction (MLR) in primary biliary cirrhosis. Clin Exp Immunol 1998; 114:94-101
Therapeutic efficacy and decreased nitrite production by bezafibrate in patients with primary biliary cirrhosis. J Gastroenterol 2005;40:157-63
Peripheral blood T-cell responses to pyruvate dehydrogenase complex in primary biliary cirrhosis: Role of antigen-presenting dendritic cells. Eur J Clin Invest 2001;31: 639-46.