Basic Research

MiR⁃155 regulates inflammatory responses and Th17/Treg imbalances in rheumatoid arthritis through the SOCS1/STAT3 pathway

  • Yuhong ZHAN ,
  • Xinjie SHAN ,
  • Jun. ZHOU
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  • *.Department of Nephrology,Xinjiang Production and Construction Corps Hospital,Urumqi 830000,China

Received date: 2023-08-11

  Online published: 2024-07-09

Abstract

Objective This research aimed to investigate the expression and mechanism of miR-155 and suppressor of cytokine signaling 1 (SOCS1) in rheumatoid arthritis (RA). Methods RT-PCR and flow cytometry were applied to detect the expression differences of miR-155, Th17, and Treg cells in peripheral blood of RA patients (RA group) and control group (HC group). Bioinformatics analysis and dual-luciferase reporter assay were conducted to investigate the regulatory relationship between miR-155 and SOCS1. CD4+T cells were isolated from peripheral blood of RA patients and transfected with miR-155 inhibitor, si-SOCS1, and their respective negative control sequences, and divided into four groups: miR-NC group, miR-155 inhibitor group, miR-155 inhibitor+si-NC group, and miR-155 inhibitor+si-SOCS1 group. The cells were treated with Th17-inducing differentiation medium, and flow cytometry was used to determine the ratio of Th17 cells in each group of CD4+T cells. Western blot was used to determine the ratio of p-STAT3/STAT3 in the cells. Results Compared to the HC group, RA patients showed increased expression of miR-155 and Th17 ratio (P < 0.01), and decreased Treg cell ratio (P < 0.01). MiR-155 could target and inhibit the expression of SOCS1. Compared to the miR-NC group, the miR-155 inhibitor group, miR-155 inhibitor+si-NC group, and miR-155 inhibitor+si-SOCS1 group showed decreased Th17 ratio and p-STAT3/STAT3 ratio (P < 0.01). Compared to the miR-155 inhibitor group, the miR-155 inhibitor+si-SOCS1 group exhibited increased Th17 ratio and p-STAT3/STAT3 ratio in CD4+T cells (P < 0.05). Conclusion Elevated expression of miR-155 in RA patients may mediate the differentiation of CD4+ T cells into Th17 cells through the SOCS1/STAT3 pathway, contributing to the imbalance of Th17/Treg cells in peripheral blood of RA patients.

Cite this article

Yuhong ZHAN , Xinjie SHAN , Jun. ZHOU . MiR⁃155 regulates inflammatory responses and Th17/Treg imbalances in rheumatoid arthritis through the SOCS1/STAT3 pathway[J]. The Journal of Practical Medicine, 2024 , 40(13) : 1791 -1796 . DOI: 10.3969/j.issn.1006-5725.2024.13.005

References

1 JANG S, KWON E J, LEE J J. Rheumatoid Arthritis: Pathogenic Roles of Diverse Immune Cells[J]. Int J Mol Sci, 2022,23(2):905. doi:10.3390/ijms23020905
2 崔家康,高青杰,马俊福,等. circ_0005276靶向miR-557调控类风湿关节炎滑膜成纤维细胞的增殖、迁移和侵袭[J]. 实用医学杂志, 2023,39(2):186-191. doi:10.3969/j.issn.1006-5725.2023.02.011
3 VAN HAMBURG J P, TAS S W. Molecular mechanisms underpinning T helper 17 cell heterogeneity and functions in rheumatoid arthritis[J]. J Autoimmun, 2018,87:69-81. doi:10.1016/j.jaut.2017.12.006
4 王艳丽,陆小霞,陈鹏,等. Tim-3在哮喘小鼠中的表达及与Th17/Treg细胞的关系[J]. 实用医学杂志, 2015,31(7):1095-1098. doi:10.3969/j.issn.1006-5725.2015.07.017
5 HILL M, TRAN N. miRNA:miRNA Interactions: A Novel Mode of miRNA Regulation and Its Effect On Disease[J]. Adv Exp Med Biol, 2022,1385:241-257. doi:10.1007/978-3-031-08356-3_9
6 BAGHERI-HOSSEINABADI Z, MIRZAEI M R, HAJIZADEH M R, et al. Plasma MicroRNAs (miR-146a, miR-103a, and miR-155) as Potential Biomarkers for Rheumatoid Arthritis (RA) and Disease Activity in Iranian Patients[J]. Mediterr J Rheumatol, 2021,32(4):324-330. doi:10.31138/mjr.32.4.324
7 MOOKHERJEE N, EL-GABALAWY H S. High degree of correlation between whole blood and PBMC expression levels of miR-155 and miR-146a in healthy controls and rheumatoid arthritis patients[J]. J Immunol Methods, 2013,400-401:106-110. doi:10.1016/j.jim.2013.10.001
8 RENRICK A N, THOUNAOJAM M C, DE AQUINO M T P, et al. Bortezomib Sustains T Cell Function by Inducing miR-155-Mediated Downregulation of SOCS1 and SHIP1[J]. Front Immunol, 2021,12:607044. doi:10.3389/fimmu.2021.607044
9 ZHANG W, CHEN C J, GUO G L. MiR-155 promotes the proliferation and migration of breast cancer cells via targeting SOCS1 and MMP16[J]. Eur Rev Med Pharmacol Sci, 2018,22(21):7323-7332. doi:10.26355/eurrev-201811-16269
10 ZHANG X F, ZHAO S R, ZHANG H. MiR-155-5p improves knee osteoarthritis rats through SOCS1-STAT3 signaling pathway[J]. Panminerva Med, 2023,65(3):433-434. doi:10.23736/s0031-0808.19.03825-4
11 EHRENTRAUT S, SCHNEIDER B, NAGEL S, et al. Th17 cytokine differentiation and loss of plasticity after SOCS1 inactivation in a cutaneous T-cell lymphoma[J]. Oncotarget, 2016,7(23):34201-34216. doi:10.18632/oncotarget.9077
12 BRITSEMMER K, URSUM J, GERRITSEN M, et al. Validation of the 2010 ACR/EULAR classification criteria for rheumatoid arthritis: slight improvement over the 1987 ACR criteria[J]. Ann Rheum Dis, 2011,70(8):1468-1470. doi:10.1136/ard.2010.148619
13 WANG W, SHAO S, JIAO Z, et al. The Th17/Treg imbalance and cytokine environment in peripheral blood of patients with rheumatoid arthritis[J]. Rheumatol Int, 2012,32(4):887-893. doi:10.1007/s00296-010-1710-0
14 MIN H K, KIM S, LEE J Y, et al. IL-18 binding protein suppresses IL-17-induced osteoclastogenesis and rectifies type 17 helper T cell/regulatory T cell imbalance in rheumatoid arthritis[J]. J Transl Med, 2021,19(1):392. doi:10.1186/s12967-021-03071-2
15 WU Y H, LIU W, XUE B, et al. Upregulated Expression of microRNA-16 Correlates with Th17/Treg Cell Imbalance in Patients with Rheumatoid Arthritis[J]. DNA Cell Biol, 2016,35(12):853-860. doi:10.1089/dna.2016.3349
16 ZHAO X, YI Y, JIANG C, et al. Gancao Fuzi decoction regulates the Th17/Treg cell imbalance in rheumatoid arthritis by targeting Foxp3 via miR-34a[J]. J Ethnopharmacol, 2023,301:115837. doi:10.1016/j.jep.2022.115837
17 YAN L, HU F, YAN X, et al. Inhibition of microRNA-155 ameliorates experimental autoimmune myocarditis by modulating Th17/Treg immune response[J]. J Mol Med (Berl), 2016,94(9):1063-1079. doi:10.1007/s00109-016-1414-3
18 LI L, SHAN W, ZHU H, et al. SJMHE1 Peptide from Schistosoma japonicum Inhibits Asthma in Mice by Regulating Th17/Treg Cell Balance via miR-155[J]. J Inflamm Res, 2021,14:5305-5318. doi:10.2147/jir.s334636
19 曹丹,汤小芳,李敏慧. miR-155-5p通过靶向抑制Sirt1影响子痫前期发生的机制[J]. 实用医学杂志, 2021,37(4):451-457. doi:10.3969/j.issn.1006-5725.2021.04.007
20 YOSHIMURA A, ITO M, MISE-OMATA S, et al. SOCS: negative regulators of cytokine signaling for immune tolerance[J].Int Immunol, 2021,33(12):711-716. doi:10.1093/intimm/dxab055
21 SOBAH M L, LIONGUE C, WARD A C. SOCS Proteins in Immunity, Inflammatory Diseases, and Immune-Related Cancer[J]. Front Med (Lausanne), 2021,8:727987. doi:10.3389/fmed.2021.727987
22 DURHAM G A, WILLIAMS J J L, NASIM M T, et al. Targeting SOCS Proteins to Control JAK-STAT Signalling in Disease[J]. Trends Pharmacol Sci, 2019,40(5):298-308. doi:10.1016/j.tips.2019.03.001
23 YAO R, MA Y L, LIANG W, et al. MicroRNA-155 modulates Treg and Th17 cells differentiation and Th17 cell function by targeting SOCS1[J]. PLoS One, 2012,7(10):e46082. doi:10.1371/journal.pone.0046082
24 YI J, WANG D, NIU X, et al. MicroRNA-155 Deficiency Suppresses Th17 Cell Differentiation and Improves Locomotor Recovery after Spinal Cord Injury[J]. Scand J Immunol, 2015,81(5):284-290. doi:10.1111/sji.12276
25 WANG D, TANG M, ZONG P, et al. MiRNA-155 Regulates the Th17/Treg Ratio by Targeting SOCS1 in Severe Acute Pancreatitis[J]. Front Physiol, 2018,9:686. doi:10.3389/fphys.2018.00686
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