BackgroundSjögren’s syndrome (SS) is a systemic autoimmune disease that affects exocrine glands and lymphoid organs. B cell hyperactivity and imbalance between T helper 17 (Th17) cells and regulatory T (Treg) cells are involved in pathogenesis of SS. Metformin, a commonly used anti-diabetic drug, is found to have immunomodulatory effect via AMP-activated protein kinase enhanced inhibition of mTOR-STAT3 signalling.ObjectivesWe examined the therapeutic effect of metformin on SS by using animal model of SS, non-obese diabetic (NOD) mice.MethodsMetformin (50 mg/kg) or vehicle (saline) was given per oral every day from 11 weeks after birth until 20 weeks. Salivary flow rate (SFR) was addressed on every 2 or 3 weeks between 11 weeks and 20 weeks. Histologic analyses of salivary gland and spleen were performed on week 20. Expression of Inflammatory cytokine was determined by immunohistochemistry analysis and real-time PCR. Flow cytometry was performed with peripheral blood to examine Th17 and Treg cells and germinal centre (GC) B cell populations. Serum immunoglobulin level was measured by enzyme-linked immunosorbent assay. Splenic cells of NOD mice were treated with metformin or vehicle in vitro and cultured for 3 days.ResultsSFRs of metformin-treated mice recovered, whereas SFRs of those treated with vehicle declined. Histologic examination of salivary gland showed decreased infiltration of lymphocytes and reduced expression of IL-6 and TNF-alpha in metformin-treated mice. Relative expression of IL-6, TNF-alpha, and IL-17 mRNA in salivary gland and spleen also declined in metformin-treated mice. Flow cytometric analysis revealed decreased Th1 and Th17 cells and increased Treg cells in peripheral blood of mice treated with metformin. In addition, GC B cells and immunoglobulin levels were reduced in peripheral blood of mice treated with metformin. Decreased Tfh cells and increased Tfr cells were observed from in vitro cultures of splenic cells treated with metformin.ConclusionsMetformin controls B cell differentiation and keeps balance between Th17 and Treg cells in NOD mice, in addition to reducing lymphocytic infiltration and inflammatory cytokine expression in salivary gland. Metformin has potential therapeutic effects on SS.References[1] Lee SY, Moon SJ, Kim EK, Seo HB, Yang EJ, Son HJ, et al. Metformin Suppresses Systemic Autoimmunity in Roquinsan/san Mice through Inhibiting B Cell Differentiation into Plasma Cells via Regulation of AMPK/mTOR/STAT3. J Immunol2017;198–2661–70.[2] Pontarini E, Lucchesi D, Bombardieri M. Current views on the pathogenesis of Sjgren’s syndrome. Curr Opin Rheumatol2017.Disclosure of InterestNone declared
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