Comparative effects of n-3, n-6 and n-9 unsaturated fatty acid-rich diet consumption on lupus nephritis, autoantibody production and CD4+ T cell-related gene responses in the autoimmune NZBWF1 mouse

• Published in: PloS one 2014-06, Vol.9 (6), p.e100255
• Main Authors: Pestka, James J, Vines, Laura L, Bates, Melissa A, He, Kaiyu, Langohr, Ingeborg
• Format: Article
• Language: English
• Subjects: Animals; Antigen presentation; Arthritis; Autoantibodies; Autoantibodies - biosynthesis; Autoimmune diseases; B7-1 Antigen - genetics; B7-1 Antigen - metabolism; Biocompatibility; Bioindicators; Biology and Life Sciences; Biomarkers; Biomedical materials; CD4 antigen; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; CD80 antigen; Cell activation; Chemokine CCL5 - genetics; Chemokine CCL5 - metabolism; Chronic conditions; Consumption; Corn oil; CTLA-4 Antigen - genetics; CTLA-4 Antigen - metabolism; CTLA-4 protein; CXCR3 protein; Cytokines; Cytokines - genetics; Cytokines - metabolism; Diet; Dietary supplements; Disease Models, Animal; Docosahexaenoic acid; Down-Regulation - drug effects; Fatty acids; Fatty Acids, Omega-3 - pharmacology; Fatty Acids, Omega-6 - pharmacology; Fatty Acids, Unsaturated - pharmacology; Female; Fish; Fish oils; Fish Oils - pharmacology; Food science; Gene expression; Gene Expression Regulation - drug effects; Genes; Glomerulonephritis; Glomerulonephritis - immunology; Glomerulonephritis - pathology; Immunoglobulin G - blood; Immunoglobulins; Inflammation; Inflammatory response; Interleukin 10; Interleukin 18; Interleukin 6; Kidney - drug effects; Kidney - metabolism; Kidney - pathology; Kidney diseases; Kidneys; Leukocytes; Lipids; Lupus; Lupus nephritis; Lupus Nephritis - blood; Lupus Nephritis - genetics; Lupus Nephritis - immunology; Lymphocytes; Lymphocytes B; Lymphocytes T; Medicine and Health Sciences; Metabolism; Mice; Nephritis; Nutrition; Oils & fats; Oleic Acid - pharmacology; Polymerase chain reaction; Polyunsaturated fatty acids; Population; Proteinuria; Proteinuria - prevention & control; Receptors, CXCR3 - genetics; Receptors, CXCR3 - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Rodents; Safflower oil; Spleen; Spleen - drug effects; Spleen - metabolism; Spleen - pathology; Systemic lupus erythematosus; Toxicology; Weight Gain - drug effects
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0100255

Mortality from systemic lupus erythematosus (SLE), a prototypical autoimmune disease, correlates with the onset and severity of kidney glomerulonephritis. There are both preclinical and clinical evidence that SLE patients may benefit from consumption of n-3 polyunsaturated fatty acids (PUFA) found in fish oil, but the mechanisms remain unclear. Here we employed the NZBWF1 SLE mouse model to compare the effects of dietary lipids on the onset and severity of autoimmune glomerulonephritis after consuming: 1) n-3 PUFA-rich diet containing docosahexaenoic acid-enriched fish oil (DFO), 2) n-6 PUFA-rich Western-type diet containing corn oil (CRN) or 3) n-9 monounsaturated fatty acid (MUFA)-rich Mediterranean-type diet containing high oleic safflower oil (HOS). Elevated plasma autoantibodies, proteinuria and glomerulonephritis were evident in mice fed either the n-6 PUFA or n-9 MUFA diets, however, all three endpoints were markedly attenuated in mice that consumed the n-3 PUFA diet until 34 wk of age. A focused PCR array was used to relate these findings to the expression of 84 genes associated with CD4+ T cell function in the spleen and kidney both prior to and after the onset of the autoimmune nephritis. n-3 PUFA suppression of autoimmunity in NZBWF1 mice was found to co-occur with a generalized downregulation of CD4+ T cell-related genes in kidney and/or spleen at wk 34. These genes were associated with the inflammatory response, antigen presentation, T cell activation, B cell activation/differentiation and leukocyte recruitment. Quantitative RT-PCR of representative affected genes confirmed that n-3 PUFA consumption was associated with reduced expression of CD80, CTLA-4, IL-10, IL-18, CCL-5, CXCR3, IL-6, TNF-α and osteopontin mRNAs in kidney and/or spleens as compared to mice fed n-6 PUFA or n-9 MUFA diets. Remarkably, many of the genes identified in this study are currently under consideration as biomarkers and/or biotherapeutic targets for SLE and other autoimmune diseases.