Original Article—Liver, Pancreas, and Biliary Tract

Journal of Gastroenterology

, Volume 45, Issue 8, pp 859-867

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

  • Teruki MiyakeAffiliated withDepartment of Gastroenterology and Metabology, Ehime University Graduate School of Medicine
  • , Sheikh Mohammad Fazle AkbarAffiliated withDepartment of Gastroenterology and Metabology, Ehime University Graduate School of MedicineDepartment of Medical Sciences, Toshiba General Hospital
  • , Osamu YoshidaAffiliated withDepartment of Gastroenterology and Metabology, Ehime University Graduate School of Medicine
  • , Shiyi ChenAffiliated withDepartment of Gastroenterology and Metabology, Ehime University Graduate School of Medicine
  • , Yoichi HiasaAffiliated withDepartment of Gastroenterology and Metabology, Ehime University Graduate School of Medicine
  • , Bunzo MatsuuraAffiliated withDepartment of Gastroenterology and Metabology, Ehime University Graduate School of Medicine
  • , Masanori AbeAffiliated withDepartment of Gastroenterology and Metabology, Ehime University Graduate School of Medicine
  • , Morikazu OnjiAffiliated withDepartment of Gastroenterology and Metabology, Ehime University Graduate School of Medicine Email author 

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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.

Keywords

NAFLD Adaptive immunity Dendritic cell HB vaccine