Intermittent Fasting Aggravates Lupus Nephritis through Increasing Survival and Autophagy of Antibody Secreting Cells in MRL/lpr Mice

• Published in: International journal of molecular sciences Vol. 21; no. 22; p. 8477
• Main Authors: Hong, Seung-Min, Lee, Jaeseon, Jang, Se Gwang, Song, Youngseok, Kim, Minjun, Lee, Jennifer, Cho, Mi-La, Kwok, Seung-Ki, Park, Sung-Hwan
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 11.11.2020; MDPI
• Subjects: Animal models; Animals; Anti-DNA antibodies; Antibodies; Antibodies, Antinuclear - immunology; Antibody-Producing Cells - immunology; Antibody-Producing Cells - pathology; Antigens; Autoantibodies; Autoantibodies - immunology; Autoantigens; Autoimmune diseases; Autophagy; Autophagy - immunology; B-Lymphocytes - immunology; B-Lymphocytes - pathology; Bone marrow; Chloroquine; Chronic conditions; Complex formation; Cytokines; Disease; Disease Models, Animal; Fasting; Fasting - physiology; Female; Kidney Glomerulus - immunology; Kidney Glomerulus - pathology; Laboratory testing; Lupus; Lupus nephritis; Lupus Nephritis - immunology; Lupus Nephritis - pathology; Lymph nodes; Lymphocytes; Lymphocytes B; Mice; Mice, Inbred MRL lpr; MRL/lpr; Nephritis; Nutrient deficiency; Phagocytosis; Plasma; Plasma cells; Proteinuria; Proteinuria - immunology; Proteinuria - pathology; Signs and symptoms; Spleen; Spleen - immunology; Spleen - pathology; Splenocytes; Systemic lupus erythematosus; systemic lupus erythematosus; fasting; autophagy; plasma cells; MRL/lpr
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21228477

Systemic lupus erythematosus (SLE) is an autoimmune disease in which the main contributors to organ damage are antibodies against autoantigens, such as double-stranded DNA (dsDNA). Calorie restriction and intermittent fasting (IF) have been shown to improve autoimmune disease symptoms in patients and animal models. Here, we tested the hypothesis that IF might improve symptoms in MRL/lpr mice, which spontaneously develop an SLE-like disease. Groups of mice were fed every other day (IF) or provided food ad libitum (controls), and various lupus-associated clinicopathological parameters were analyzed for up to 28 weeks. Contrary to expectations, anti-dsDNA antibody levels, immune complex deposition in the kidney, and glomerular injury were higher in the IF group than the control group, although there were no differences in spleen and lymph node weights between groups. Proteinuria was also worsened in the IF group. IF also increased the abundance of B cells, plasmablasts, and plasma cells and elevated autophagy in plasma cells in the spleen and lymph nodes. Secretion of anti-dsDNA antibody by splenocytes in vitro was reduced by chloroquine-induced inhibition of autophagy. These results suggest that IF exacerbates lupus nephritis in MRL/lpr mice by increasing autoantibody immune complex formation.