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.
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