The effect of dietary phytoestrogen content on the development of systemic lupus erythematosus in the MRL/lpr mouse.

Abstract

Abstract Systemic lupus erythematosus is a prototypical autoimmune disease, characterized by the loss of immune cell tolerance to self-antigens, and the subsequent production of autoantibodies leading to multi-organ damage. SLE is an incurable, highly variable autoimmune disease that most often affects women of child-bearing age. We investigated the effects of three standard commercial diets with varying phytoestrogen content on the development of lupus in female MRL/lpr mice. The diets include Harlan 2018 which contains soybean meal, Teklad 7013 which contains both soy and alfalfa, and Research Diets Inc. D11112226 (RD) purified ingredients diet, containing no measurable phytoestrogens. Mice fed the 2018 diet developed severe glomerulonephritis with high levels of complement C3 protein deposition and moderate IgG immune-complex deposition, while mice fed the RD diet developed minimal evidence of renal damage and protein deposition. The mice fed the RD diet, however, had increased levels of multiple pro-inflammatory cytokines, while immune cell populations remained unchanged. Immunofluorescence revealed distinct infiltrating cellular phenotypes in the kidney, dependent on dietary source. Splenocyte miRNA-148a was markedly elevated in mice fed the 2018 and 7013 diets, while circulating miRNA values were not statistically different. Our results suggest that dietary isoflavones can worsen the development of glomerulonephritis due to enhanced immune complex protein deposition and altered cellular infiltration phenotypes. Our results also support that each organ system must be evaluated independently, and that what is measured in circulation does not necessarily reflect what is occurring in disease target organs.