MicroRNA-10b promotes arthritis development by disrupting CD4+ T cell subtypes

Jiajie Tu; Dafei Han; Yilong Fang; Haifeng Jiang; Xuewen Tan; Zhen Xu; Xinming Wang; Wenming Hong; Tao Li; Wei Wei

doi:10.1016/j.omtn.2021.12.022

MicroRNA-10b promotes arthritis development by disrupting CD4⁺ T cell subtypes

Mol Ther Nucleic Acids. 2021 Dec 18:27:733-750. doi: 10.1016/j.omtn.2021.12.022. eCollection 2022 Mar 8.

Authors

Jiajie Tu^{1

2}, Dafei Han¹, Yilong Fang¹, Haifeng Jiang¹, Xuewen Tan¹, Zhen Xu¹, Xinming Wang¹, Wenming Hong¹, Tao Li³, Wei Wei¹

Affiliations

¹ Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-Inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-Inflammatory and Immune Medicine, Hefei, China.
² Department of Gynecology, Shenzhen Second People's Hospital/The First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, China.
³ Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

Abstract

Rheumatoid arthritis (RA) is an inflammation-involved disorder and features the disruption of CD4⁺ T lymphocytes. Herein, we describe that microRNA-10b-5p (miR-10b) promotes RA progression by disrupting the balance between subsets of CD4⁺ T cells. MiR-10b-deficient mice protected against collagen antibody-induced arthritis (CAIA) model. RNA sequencing results indicated that disordered genes in miR-10b^-/- CAIA model are closely associated with CD4⁺ T cells differentiation. Moreover, miR-10b mimics promoted Th1/Th17 and suppressed Th2/Treg cells differentiation, whereas miR-10b inhibitor induced contrary effects. In addition, GATA3 and PTEN was confirmed as two targets of miR-10b, and GATA3 siRNA could increase Th1 and reduce Th2 cells meanwhile PTEN siRNA could increase Th17 and decrease Treg cells. Furthermore, miR-10b inhibitor significantly ameliorated collagen-induced arthritis (CIA) development by attenuating the dysfunctional CD4⁺ T cell subpopulations. The present findings suggest that miR-10b could disrupt the balance of CD4⁺ T subsets, while suppressed miR-10b could attenuate the severity of experimental arthritis, which provided us a novel mechanistic and therapeutic insight into the RA.

Keywords: GATA3; PTEN; RA; Th1/2; Th17/Treg; miR-10b.