Dendritic cell activation, phagocytosis and CD69 expression on cognate T cells are suppressed by n-3 long-chain polyunsaturated fatty acids.
Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are bioactive n-3 long-chain polyunsaturated fatty acids (LCPUFAs) in fish oil that exert immunosuppressive effects. A significant amount of literature shows that n-3 LCPUFAs suppress dendritic cell (DC) function in vitro; however, few studies have determined if the effects are emulated at the animal level. In this study, we first focused on the functional consequences of 5% (weight/weight) fish oil on splenic CD11c(+) DCs. Administration of n-3 LCPUFAs, modelling human pharmacological intake (2% of total kcal from EPA,1·3% from DHA), to C57BL/6 mice for 3 weeks reduced DC surface expression of CD80 by 14% and tumour necrosis factor-α secretion by 29% upon lipopolysaccharide stimulation relative to a control diet. The n-3 LCPUFAs also significantly decreased CD11c(+) surface expression and phagocytosis by 12% compared with the control diet. Antigen presentation studies revealed a 22% decrease in CD69 surface expression on transgenic CD4(+) T lymphocytes activated by DCs from mice fed fish oil. We then determined if the functional changes were mechanistically associated with changes in lipid microdomain clustering or plasma membrane microviscosity with n-3 LCPUFAs, as reported for B and T lymphocytes. Fish oil administration to mice did not influence cholera-toxin induced lipid microdomain clustering or microviscosity, even though EPA and DHA levels were significantly elevated relative to the control diet. Overall, our data show that n-3 LCPUFAs exert immunosuppressive effects on DCs, validating in vitro studies. The results also show that DC microdomain clustering and microviscosity were not changed by the n-3 LCPUFA intervention used in this study.
Department of Biochemistry and Molecular Biology, East Carolina University, Greenville, NC, USA.
Heather
H
Teague
Benjamin Drew
BD
Rockett
Mitchel
M
Harris
David A
DA
Brown
Saame Raza
SR
Shaikh
D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000378:metabolism*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D005395:Fish Oils / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010587:Phagocytosis; D013601:T-Lymphocytes / Q000276:immunology*; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D004042:Dietary Fats, Unsaturated; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D037181:Lectins, C-Type; D000099192:CD69 Antigens