期刊
FRONTIERS IN IMMUNOLOGY
卷 11, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2020.01796
关键词
systemic lupus erythematosus; NZBWF1; omega-3 fatty acid; Omega-3 Index; highly unsaturated fatty acid; silica; docosahexaenoic acid; precision nutrition
类别
资金
- NIH [ES027353, F31ES030593, T32ES007255]
- Lupus Foundation of America
- USDA National Institute of Food and Agriculture Hatch Projects [1020129, UTA-01407, UTA-01456]
- Dr. Robert and Carol Deibel Family Endowment
Lupus is a systemic autoimmune disease typified by uncontrolled inflammation, disruption of immune tolerance, and intermittent flaring - events triggerable by environmental factors. Preclinical and clinical studies reveal that consumption of the marine omega-3 highly unsaturated fatty acids (HUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) might be used as a precision nutrition intervention to lessen lupus symptoms. The anti-inflammatory and pro-resolving effects of omega-3 HUFAs are inextricably linked to their presence in membrane phospholipids. The omega-3 HUFA score, calculated as [100 x (omega-3 HUFAs/(omega-3 HUFAs + omega-6 HUFAs))] in red blood cells (RBCs), and the Omega-3 Index (O3I), calculated as [100 x ((DHA+EPA)/total fatty acids)] in RBCs, are two biomarkers potentially amenable to relating tissue HUFA balance to clinical outcomes in individuals with lupus. Using data from three prior preclinical DHA supplementation studies, we tested the hypothesis that the omega-3 HUFA score and the O3I inversely correlate with indicators of autoimmune pathogenesis in the cSiO(2)-triggered lupus flaring model. The three studies employed both low and high fat rodent diets, as well as more complex diets emulating the U.S. dietary pattern. The omega-3 HUFA scores in RBCs were comparatively more robust than the O3I at predicting HUFA balances in the kidney, liver, spleen, and lung. Importantly, increases in both the omega-3 HUFA score (>40%) and the O3I (>10%) were strongly associated with suppression of cSiO(2)-triggered (1) expression of interferon-regulated genes, proinflammatory cytokine production, leukocyte infiltration, and ectopic lymphoid structure development in the lung, (2) pulmonary and systemic autoantibody production, and (3) glomerulonephritis. Collectively, these findings identify achievable omega-3 HUFA scores and O3I thresholds that could be targeted in future human intervention studies querying how omega-3 HUFA consumption influences lupus and other autoimmune diseases.
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