Session Type: Poster Session D
Session Time: 8:30AM-10:30AM
Background/Purpose: Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease characterized by persistent inflammation and production of autoantibodies, which deposit within numerous tissues leading to systemic damage. Multiple studies have suggested a link between obesity, metabolic syndrome, and SLE. Our recent data has shown that fat-diet-induced obesity exacerbates lupus symptoms in lupus prone mice, suggesting a unique role of obesity in autoimmune pathogenesis. This study is to probe the role of follicular T helper (Tfh) cells and T regulatory (Treg) cells in fat-diet associated lupus development in MRL/lpr lupus prone mice.
Methods: Forty MRL/lpr mice were fed and grouped in a regular diet (RD, 10% calories from fat) or high fat diet (HFD, 60% calories from fat). Their body weights and skin lesions were recorded weekly. Urine protein was assessed weekly by Bradford assay. Blood was collected monthly for anti-dsDNA antibody and anti-nuclear antibody (ANA) detection. At week 14, mice were euthanized, their spleen were measured and weighed. Kidney and skin biopsy were embedded in paraffin and tissue sections for H&E and PAS staining to detect lupus histopathological lesions and quantified as kidney index and histological skin score. B cells (CD19+), germinal center B cells (GC-B cell, GL7+CD19+), plasma cells (CD20–CD138+), Tfh cells (CD4+CXCR5+ICOS+), and Treg cells (CD4+FoxP3+) were examined in splenocytes by flow cytometry and confirmed in the spleen slides using immunofluorescent staining.
Results: The HFD group demonstrated a significant increase in mouse body weight by week 3 and continued until week 14 compared to RD group (p< 0.05 to p< 0.01). SLE features, such as skin lesions on the dorsum of neck (p< 0.05), splenomegaly (p< 0.05), and proteinuria developed significantly earlier and more severe in HFD group than RD group. Increased of acute/chronic index of kidney and increased levels of anti-dsDNA antibody were also observed in HFD group. However, ANA level was comparable between HFD group and RD group. At week 14, the Immune cells such as the frequencies of GC-B cells and plasma cells were significantly higher in the spleens of HFD group than RD group (p< 0.05). There was no difference in the frequencies of CD4+ and CD8+ T cells in the spleens of HFD group and RD group. Significant increase of Tfh cells and enlarged germinal centers were observed in the spleen of HFD group (p< 0.05). The ratio of Tfh/Treg in the spleen of HFD mice was also significantly increased compared to the RD group (p< 0.05).
Conclusion: Our results show that high fat diet induced an accelerated and more severe form of lupus development and imbalance of Tfh/Treg cells in MRL/lpr mice. This indicates that HFD affects T cell homeostasis and exacerbates the autoimmunity in lupus development. Modulations of diet or restoring the balance between Tfh and Treg cells may improve both lupus symptoms and outcomes in genetically predisposed SLE patients.
To cite this abstract in AMA style:Patel R, Posas-Mendoza T, Meng J, Shi X, Dhulipala S, Hille C, Hellmers L, Quinet R, Davis W, Zakem J, Keshavamurthy C, You Z, Zhang X. Imbalance Between T Follicular Cells and T Regulatory Cells Involved in High Fat-Diet Associated Lupus Development in MRL/lpr Mice [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/imbalance-between-t-follicular-cells-and-t-regulatory-cells-involved-in-high-fat-diet-associated-lupus-development-in-mrl-lpr-mice/. Accessed September 29, 2022.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/imbalance-between-t-follicular-cells-and-t-regulatory-cells-involved-in-high-fat-diet-associated-lupus-development-in-mrl-lpr-mice/