Targeting the Progression of Lupus-Like Disease in Humanized Mouse Model by Specific Dietary Components

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with a number of immunological aberrations in the mechanisms of innate and adaptive immune responses. Spontaneous and induced mouse models of the disease have contributed significantly to the advancement in lupus treatments. The involvement of humanized models, engrafted with lupus patients' immune cells, represented the possibility to study the development of SLE. In the current research, we engrafted NSG/Rag2-γc- mice with PBMCs from lupus patients and put the mice on specific diet composed of extra amounts of methyl-containing micronutrients and cofactors which are key participants in the DNA methylation processes. The results showed a decrease in anti-dsDNA IgG antibody and in proteinuria levels, less glomerular proliferation and protected renal structures in all mice put on the supplemented diet compared to humanized mice fed with the control diet. The observed therapeutic effect may be related to possible alterations in the methylation level and to targeted suppression of gene expression in the immune cells, which correlate negatively with the development of the clinical SLE characteristics. These findings point to the significant immunomodulating role of methyl donors in human models of SLE and represent new therapeutic opportunities with clinical potential.