Abstract
Accumulating evidence suggests that cholesterol accumulation in leukocytes is causally associated with the development of autoimmune diseases. However, the mechanism by which fatty acid composition influences autoimmune responses remains unclear. To determine whether the fatty acid composition of diet modulates leukocyte function and the development of systemic lupus erythematosus, we examined the effect of eicosapentaenoic acid (EPA) on the pathology of lupus in drug-induced and spontaneous mouse models. We found that dietary EPA supplementation ameliorated representative lupus manifestations, including autoantibody production and immunocomplex deposition in the kidneys. A combination of lipidomic and membrane dynamics analyses revealed that EPA remodels the lipid composition and fluidity of B cell membranes, thereby preventing B cell differentiation into autoantibody-producing plasma cells. These results highlight a previously unrecognized mechanism by which fatty acid composition affects B cell differentiation into autoantibody-producing plasma cells during autoimmunity, and imply that EPA supplementation may be beneficial for therapy of lupus.
Highlights
Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease that affects multiple organs, and it is characterized by autoantibody production
We confirmed that similar amount of palmitate intake does not affect the pathology of lupus compared to a diet without additional fatty acid
Consistent with a previous report [24], the epicutaneous application of IMQ resulted in splenomegaly, lymphadenopathy, increased deposition of immunoglobulin G (IgG) and complement component 3 (C3) in kidney glomeruli, and elevated levels of anti-nuclear (ANA), anti-double stranded DNA and anti-histone autoantibodies (Figures 1D, E and Figure S1)
Summary
Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease that affects multiple organs, and it is characterized by autoantibody production. As the concordance rate for SLE in identical twins is only 25-60%, this complex disease is caused by both genetic and environmental factors [1]. Patients with SLE have increased risk of atherosclerosis, and cardiovascular disease is Eicosapentaenoic Acid Attenuates Lupus Autoimmunity one of the major causes of morbidity and mortality in these patients [2]. Recent genome-wide association studies and expression quantitative trait loci analyses have revealed that genes involved in lipid metabolism increase the susceptibility to autoimmune diseases such as rheumatoid arthritis and SLE [4,5,6]. The molecular mechanism by which lipid metabolism influences the pathology of SLE is unclear
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