Session Information
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: Systemic lupus erythematosus (SLE) is a multi-systemic autoimmune disease characterized by B cell hyperactivation and the production of autoantibodies. Histone deacetylase, Sirtuin1 (Sirt1) has been shown to play a role in regulation of inflammation. Sirt1 deficiency results in the development of lupus-like disease in mice, including the production of anti-nuclear antibody.Resveratrol (trans-3,4′,5-trihydroxystilbene), a natural polyphenolic phytoalexins, is a potent activator of Sirt1. Our study was conducted to determine the expression of Sirt1 in B cells in SLE patients and further test the effects of resveratrol on B cell activation and auto-Ab production in pristane-induced mouse lupus model.
Methods: Flow cytometry and real-time PCR were used to analyze the expression of Sirt1. Sirt1 signaling was modulated with the Sirt1 agonist resveratrol. BALB/c mice were given 0.5 ml of pristane on day 1 by intraperitoneal injection to induce the lupus-like disease and on day 2 the mice received various doses of resveratrol. CD19+ B cells were isolated from the spleen mononuclear cells of the pristane-induced lupus mice and cultured with or without resveratrol in vitro for 3-5 days and B cell activation, plasma B cell differentiation and Prdm1 gene expression were assessed by flow cytometry or real-time PCR.
Results: The expression of Sirt1 in CD19+B cells of SLE patients was significantly decreased when compared to healthy donors (p=0.0071). The expression of Sirt1 negatively correlated with CD19+ B cell frequencies (p=0.0008). In pristane-induced lupus mice, Sirt1 activator-resveratrol dramatically decreased the expression of CD69, CD80, CD86 expression of B lymphocytes in a dose-dependent manner. Resveratrol significantly inhibited CDl38+ plasma cell differentiation of B lymphocytes after stimulation with LPS plus anti-CD40 antibody. Finally, resveratrol significantly inhibited the expression of PRDM1(gene encoding Blimp-1) mRNA in B-cells.
Conclusion: Sirt1 is downregulated in SLE patients. The use of resveratrol, Sirt1 agonist may present a novel approach for treatment of SLE by inhibiting B cell activation and plasma cell differentiation.
To cite this abstract in AMA style:
Wang T, Song X, Luo X, Li M, Zeng X. Resveratrol Regulates Sirt1 to Control B Cells Activation and Plasma B Cells Differentiation [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/resveratrol-regulates-sirt1-to-control-b-cells-activation-and-plasma-b-cells-differentiation/. Accessed .« Back to 2017 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/resveratrol-regulates-sirt1-to-control-b-cells-activation-and-plasma-b-cells-differentiation/