Type 2 innate lymphoid cells regulation by regulatory T cells attenuates atherosclerosis. (August 2020)

• Record Type: Journal Article
• Authors: Gao, Xiaonan; Lin, Jibin; Zheng, Yuqi; Liu, Shangwei; Liu, Chengxing; Liu, Tianxiao; Wang, Boyuan; He, Shaolin; Li, Dazhu
• Is Part Of: Journal of molecular and cellular cardiology. Volume 145(2020)
• Page Start: 99
• Page End: 111
• Publication Date: 2020-08
• Subjects: Atherosclerosis -- Regulatory T cells -- ILC2s -- Innate lymphoid cells -- IL-13; 7-AAD 7-Aminoactinomycin -- ApoE−/− Apolipoprotein E-deficient -- α-SMA Alpha-smooth muscle actin -- CD Cluster of differentiation -- ECM experimental cerebral malaria -- ELISA Enzyme-linked immunosorbent assay -- FACS Fluorescence-activated cell sorting -- FBS Fetal bovine serum -- Foxp3 Forkhead box P3 protein (aka scurfin) -- GFP Green fluorescence protein -- HFD High fat diet -- IL Interleukin -- ILC Innate lymphoid cell -- ILC2s Type 2 (Group 2) innate lymphoid cells -- IFN-γ Interferon-γ -- ICOS Inducible T-cell costimulator (aka CD278) -- ICOS-L ICOS ligand (aka CD275) -- MACS Magnetic-activated cell sorting -- NH Natural helper -- NK natural killer -- OCT optimal cutting temperature -- PBS Phosphate-buffered solution -- PaLN Para-aortic lymph node -- PMA Phorbol 12-myristate 13-acetate -- Rag1−/− Recombination activating gene 1 deficient -- RORγt Retinoid related orphan nuclear receptor-γt -- Treg cell Regulatory T cell -- TGF-β Transforming growth factor beta -- Th1 Type 1 helper T cell -- Th2 Type 2 helper T cell -- VSMCs vascular smooth muscle cells; Cardiology -- Periodicals; Heart Diseases -- Periodicals; Molecular Biology -- Periodicals; Cardiologie -- Périodiques; Cardiology; Electronic journals; Periodicals; 616.12
• DOI: 10.1016/j.yjmcc.2020.05.017
• Languages: English
• ISSNs: 0022-2828

Abstract

Abstract: Regulatory T cells (Tregs) have been shown to attenuate the development and progression of atherosclerosis; however, the exact mechanism is still unclear. In our study, Tregs were adoptively transferred into ApoE −/− mice, and type 2 innate lymphoid cells (ILC2s) were expanded by the IL-2/Jes6-1 complex or depleted by anti-CD90.2 mAb in ApoE −/- Rag1 −/− mice to study their effects on atherosclerosis. Then, Tregs were cocultured with ILC2s in vitro to analyze ILC2s number and IL-13 production. In vivo, ApoE −/- Rag1 −/− mice were treated with activated Tregs with or without anti-CD90.2 mAb to explore whether Tregs reduced atherosclerosis through ILC2s. Finally, neutralizing antibodies and Transwell assay were used to investigate how Tregs regulate ILC2s. Our results show that both Tregs and ILC2s reduce atherosclerosis lesions and macrophage infiltration. Moreover, Tregs effectively expanded the number of ILC2s and increased their production of IL-13 in vivo and in vitro . Furthermore, the reductions in plaque size and macrophage infiltration by Tregs were partly reversed by anti-CD90.2 mAb. Mechanistically, our data reveal that IL-10, TGF-β and cell-cell contacts are required for Tregs-ILC2s regulation. These results show that Tregs may play a partial protective role against atherosclerosis by expanding the number of ILC2s and consequently increasing IL-13 production. Graphical abstract: Unlabelled Image Highlights: Tregs can modulate the number and function of type 2 innate lymphoid cells. Tregs and type 2 innate lymphoid cells reduce atherosclerotic lesions. Tregs protect from atherosclerosis partly through type 2 innate lymphoid cells.