Travel-Induced Stress at Varying Ages Modulates the Pathogenesis of Autoimmunity in Female Lupus Mice

Date

2022

Authors

Dinh, Viet
Chaudhari, Sarika

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Abstract

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that causes inflammation throughout the body, notably in the kidneys. Inflammatory flares that occur during the pathogenesis of SLE increase morbidity in humans and are associated with stress and environmental factors. Heat shock proteins (HSPs) are chaperone proteins that are elevated in the stressful conditions, especially HSP90 which is increased in subsets of SLE patients. HSP90 is also correlated with interleukin (IL)-6, a proinflammatory cytokine known to stimulate autoimmune processes in many diseases including SLE. The lupus mice used in our lab travel to our university from Bar Harbor, ME. However, it is not known if this travel period induces stress on these mice that significantly affects the pathogenesis of SLE and renal damage. Likewise, it is unknown if the age at which the mice travel also predicts outcomes of the disease. Based on this, we hypothesize that stressors that occur early in life have a greater impact on the pathogenesis of SLE and renal inflammation than stressors that occur during adulthood in lupus-prone mice. We used female NZBWF1 mice - an established model of SLE - that traveled to our university at 6 weeks of age (pre-pubertal stage) or at 19 weeks of age (mature adult stage) to compare the effects of travel at different ages of life. At 30 weeks of age, they were placed in metabolic cages weekly to collect urine samples. Upon reaching 35 weeks of age, a point at which these mice usually develop severe lupus symptoms, we collected blood samples, euthanized the mice, and collected tissues. Urine, plasma, and homogenized right kidneys were analyzed via ELISA to compare various biomarkers, including double-stranded (ds)DNA autoantibodies (a hallmark of SLE), urinary albumin (a marker of renal injury), IL-6, and HSP90. No differences were found in plasma dsDNA autoantibodies between mice that traveled in younger life vs. in adulthood (Young: 6.0e5 ± 8.4e4 vs. Adults: 5.2e5 ± 7.6e4 U/mL; p=0.6930). Likewise, no differences were found in urinary albumin between these groups (Young: 1.2e7 ± 3.2e6 vs. Adults: 1.0e7 ± 8.4e6 ng/mL; p=0.8208). In mice that traveled as adults, IL-6 was significantly higher in plasma (Young: 195.8 ± 87.4 vs. Adults: 826.7 ± 130.0 pg/mL; p=0.0096) and in kidneys (Young: 177.1 ± 60.6 vs. Adults: 798.1 ± 166.5 pg/mL; p=0.0002). Levels of plasma HSP90 were lower in mice that traveled as adults (Young: 152.1 ± 23.4 vs. Adults: 65.70 ± 8.60 ng/mL; p=0.0302). In conclusion, our data indicate that mice subjected to travel-induced stress as adults developed higher levels of plasma and renal IL-6 and lower levels of plasma HSP90 at 35 weeks of age. We will continue to evaluate these outcomes in more mice and further data will expand on these findings, which will act as an important steppingstone for furthering our understanding of how environmental stressors play a role in the progression of autoimmunity well into adulthood.

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Research Appreciation Day Award Winner - 2022 School of Biomedical Sciences Oral Presentation - 1st Place

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