THU0242 MIR-326 OVEREXPRESSION IN T CELLS BREAKS TH17/TREG BALANCE IN MRL/LPR MICE
Authors: Yuan Xia, Xuan Fang, Nan Xiang, Xiaojuan Dai, LI Jin, LI Xiaomei, Jinhui Tao, LI Xiangpei
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organs leading to tissue damage<sup>1</sup>. T lymphocytes have been recognized as key contributors to disease pathogenesis<sup>2</sup>. Inflammatory Th17 subsets promote inflammation, while defects in regulatory T cells (Tregs) lead to unchecked immune responses<sup>3</sup>. Emerging data suggest that single miR species can profoundly alter the phenotype and outcome of immune responses in SLE<sup>4</sup>. Objectives: we describe a role for miR-326 in driving deregulation of Th17/Treg balance in lupus mouse and highlight therapeutic advances of miR-326. <h3>Methods:</h3> 3 groups of female MRL/lpr mice were injected with lentivirus-miR-326 (LV-326) or lentivirus-miR-326 specific inhibitor (LV-sponge) to increase or inhibit miR-326 expression, respectively, and lentivirus-no-encoding (LV-ctrl) as control, 10 mice per group. The percentage of Th17 cells and Tregs in spleen CD4<sup>+</sup> T cells and kidney were detected by flow cytometry. The levels of serum cytokine (IL-17A, IFN-γ, TGF-β) were detected by CBA. Urinary collections (24 h) were collected and assessed for albumin using ELISA. Immunohistochemistry labeled kidney IL-17A and TGF-β expression. Differences between groups were analyzed by SPSS software. <h3>Results:</h3> Day 7 analysis of differentiation of Th17 cells and Tregs in spleen after injection of lentivirus showed an increased percentage of Th17 in LV-326 mice, while reduction of percentage of Tregs in these mice. Testing the serum cytokines revealed that the significantly increased levels of IL-17A and IFN-γ in LV-326 mice, and decreased in LV-sponge mice, no different has been found in TGF-β between the groups. Moreover, LV-326 mice showed higher levels of 24h urinary albumin than LV-sponge and LV-ctrl mice in day 7 after injection of lentivirus. The lentivirus-miR-326 injection promoted the infiltration of Th17 cells and simultaneously increased the expression of IL-17A in kidney, no different has been found of TGF-β. <h3>Conclusion:</h3> Our data reveal that miR-326 overexpression increased the differentiation of Th17 cells and decreased the differentiation of Tregs, and accelerated the renal injury in MRL/lpr mice. These suggest that miR-326 may play a catalytic role in the development of lupus-like changes in lupus model mouse by breaks Th17/Treg balance. <h3>References:</h3> [1] Tsokos, G.C. Systemic lupus erythematosus. N Engl J Med365, 2110-2121 (2011). [2] Moulton, V.R. et al. Pathogenesis of Human Systemic Lupus Erythematosus: A [3] Cellular Perspective. Trends Mol Med 23, 615-635 (2017). [4] Suarez-Fueyo, A., Bradley, S.J. &amp; Tsokos, G.C. T cells in Systemic Lupus Erythematosus. Curr Opin Immunol 43, 32-38 (2016). [5] Lam, I.K.Y., Chow, J.X., Lau, C.S. &amp; Chan, V.S.F. MicroRNA-mediated immune regulation in rheumatic diseases. Cancer Lett 431, 201-212 (2018). <h3>Disclosure of Interests:</h3> None declared