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Impaired dendritic cell functions disrupt antigen-specific adaptive immune responses in mice with nonalcoholic fatty liver disease

  • Original Article—Liver, Pancreas, and Biliary Tract
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Abstract

Background/aims

The magnitude of antigen-specific immunity was assessed in a murine model of nonalcoholic fatty liver diseases (NAFLD). Because antigen-specific immunity was diminished in NAFLD mice, the underlying mechanisms were evaluated through analysis of the functions of antigen-presenting dendritic cells (DC) and other immunocytes.

Methods

For 12 weeks, NAFLD mice received a high-fat (60%) and high-calorie (520 kcal/100 g) diet. C57BL/6 mice (controls) received a standard diet. NAFLD mice and control mice were immunized with hepatitis B vaccine containing hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg). Antibody to HBsAg (anti-HBs), HBsAg and HBcAg-specific cellular immune response and functions of whole spleen cells, T lymphocytes, B lymphocytes and spleen DCs of NAFLD and control mice were assessed in vitro.

Results

Levels of anti-HBs and the magnitude of proliferation of HBsAg and HBcAg-specific lymphocytes were significantly lower in NAFLD mice than control mice (P < 0.05). The spleen cells of NAFLD mice produced significantly higher levels of inflammatory cytokines (P < 0.05) and exhibited significantly increased T cell proliferation compared with control mice (P < 0.05). However, the antigen processing and presenting capacities of spleen DCs were significantly decreased in NAFLD mice compared with control mice (P < 0.05). Palmitic acid, a saturated fatty acid, caused diminished antigen processing and presenting capacity of both murine and human DCs.

Conclusions

Nonalcoholic fatty liver disease mice exhibit decreased magnitudes of antigen-specific humoral and cellular immune responses. This effect is mainly, if not solely, due to impaired antigen processing and presentation capacities of DC.

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Acknowledgments

We would like to thank the Integrated Centre for Science, Shigenobu Station, Ehime University for animal management.

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Authors and Affiliations

  1. Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, 791-0295, Japan

    Teruki Miyake, Sheikh Mohammad Fazle Akbar, Osamu Yoshida, Shiyi Chen, Yoichi Hiasa, Bunzo Matsuura, Masanori Abe & Morikazu Onji

  2. Department of Medical Sciences, Toshiba General Hospital, Tokyo, Japan

    Sheikh Mohammad Fazle Akbar

Authors
  1. Teruki Miyake
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  2. Sheikh Mohammad Fazle Akbar
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  3. Osamu Yoshida
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Correspondence to Morikazu Onji.

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Miyake, T., Akbar, S.M.F., Yoshida, O. et al. Impaired dendritic cell functions disrupt antigen-specific adaptive immune responses in mice with nonalcoholic fatty liver disease. J Gastroenterol 45, 859–867 (2010). https://doi.org/10.1007/s00535-010-0218-4

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  • DOI: https://doi.org/10.1007/s00535-010-0218-4

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