Circulating Exosomes Control CD4+ T Cell Immunometabolic Functions via the Transfer of miR-142 as a Novel Mediator in Myocarditis

Park, Sun; Wang, Naixin; Zhao, Peng; Wang, Chao; Li, Hairu; Chen, Qi; Mang, Ge; Wang, Weiwei; Fang, Shaohong; Du, Guoqing; Zhang, Maomao; Tian, Jiawei

doi:10.1016/j.ymthe.2020.08.015

Cited by 26 publications

(13 citation statements)

References 64 publications

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“…Additionally, in Sun et al ’s study, the injection of serum exosomes from mice with EAM induced global CD4 + T cell activation and cardiac inflammation. Mechanistically, circulating exosomes from mice with EAM were selectively loaded with abundant miR-142, which was confirmed by luciferase assays to regulate CD4 + T cell dysfunction and glycolytic reprogramming by targeting methyl-CpG binding domain protein 2 (MBD2) and suppressor of cytokine signaling 1 (SOCS1) ( 104 ). Further, other studies have reported that miR-590-3p and miR-141-3p can also play a role in EAM by reducing cardiac inflammation; however, more detailed mechanisms have yet to be elucidated ( 101 , 102 ).…”

Section: Resultsmentioning

confidence: 96%

The role of non-coding RNAs in myocarditis: a narrative review

Liu¹,

Hu²,

Lü³

et al. 2022

Ann Transl Med

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Background and Objective: Myocarditis is a heterogeneous disease that can lead to acute heart failure, dilated cardiomyopathy (DCM), and sudden death. However, the knowledge of the precise molecular mechanisms of myocarditis is fairly limited. In recent years, non-coding RNAs (ncRNAs) have been demonstrated to be involved in many physiological and pathological processes in myocarditis and to have the potential to be used as novel diagnostic and therapeutic strategies for myocarditis. This review summarizes the role of ncRNAs in myocarditis and discusses their potential as noninvasive biomarkers and therapeutic targets for myocarditis.Methods: Literature on ncRNAs and myocarditis published in PubMed was extensively reviewed for analysis and discussion.

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Section: Resultsmentioning

confidence: 96%

The role of non-coding RNAs in myocarditis: a narrative review

Liu¹,

Hu²,

Lü³

et al. 2022

Ann Transl Med

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“…Other biomolecules interacted with MBD2 are broadly reported in PH relevant research. For instance, MBD2 is believed to repress the MYC gene transcription, thus suppressing glycolysis ( 41 , 42 ), and MBD2 is also reported to interplay with non-coding RNA related to PH ( 23 ). Whereas in other cases, MBD2 is also associated with many proliferative diseases.…”

Section: Discussionmentioning

confidence: 99%

Increased Methyl-CpG-Binding Domain Protein 2 Promotes Cigarette Smoke-Induced Pulmonary Hypertension

Huang

et al. 2022

Front. Oncol.

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Pulmonary hypertension (PH) is a chronic vascular proliferative disorder. While cigarette smoke (CS) plays a vital part in PH related to chronic obstructive pulmonary disease (COPD). Methyl-CpG-Binding Domain Protein 2 (MBD2) has been linked to multiple proliferative diseases. However, the specific mechanisms of MBD2 in CS-induced PH remain to be elucidated. Herein, the differential expression of MBD2 was tested between the controls and the PH patients’ pulmonary arteries, CS-exposed rat models’ pulmonary arteries, and primary human pulmonary artery smooth muscle cells (HPASMCs) following cigarette smoke extract (CSE) stimulation. As a result, PH patients and CS-induced rats and HPASMCs showed an increase in MBD2 protein expression compared with the controls. Then, MBD2 silencing was used to investigate the function of MBD2 on CSE-induced HPASMCs’ proliferation, migration, and cell cycle progression. As a consequence, CSE could induce HPASMCs’ increased proliferation and migration, and cell cycle transition, which were suppressed by MBD2 interference. Furthermore, RNA-seq, ChIP-qPCR, and MassARRAY were conducted to find out the downstream mechanisms of MBD2 for CS-induced pulmonary vascular remodeling. Subsequently, RNA-seq revealed MBD2 might affect the transcription of BMP2 gene, which furtherly altered the expression of BMP2 protein. ChIP-qPCR demonstrated MBD2 could bind BMP2’s promotor. MassARRAY indicated that MBD2 itself could not directly affect DNA methylation. In sum, our results indicate that increased MBD2 expression promotes CS-induced pulmonary vascular remodeling. The fundamental mechanisms may be that MBD2 can bind BMP2’s promoter and downregulate its expression. Thus, MBD2 may promote the occurrence of the CS-induced PH.

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“…Circulating exosomes can mediate immune responses and induce either immunogenic or tolerogenic responses in different environments. In autoimmune diseases such as MS in man, 3 and rodent models of autoimmune myocarditis, 5 circulating exosomes promote autoreactive T cell responses. We assumed that circulating exosomes in EAU in rodents would also enhance autoreactive T cell immunity.…”

Section: Discussionmentioning

confidence: 99%

“…Human lung transplant recipients undergoing rejection had circulating exosomes with lung self‐antigens, K‐alpha 1 tubulin and collagen V. Immunisation of C57BL/6 mice with these exosomes induced obliterative airway disease 4 . Circulating exosomes isolated from murine experimental autoimmune myocarditis (EAM) initiated T cell pathological immune responses and enhanced EAM via cargo miR‐142 5 …”

Section: Introductionmentioning

confidence: 99%

Vaccination with circulating exosomes in autoimmune uveitis prevents recurrent intraocular inflammation

Jiang

Yun

Kaplan

et al. 2021

Clinical Exper Ophthalmology

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Background Exosomes participate in intercellular communication and act as important molecular vehicles in the regulation of numerous physiological and pathological processes, including autoimmune development. The role of circulating exosomes in the development of autoimmune uveitis is unknown. In this study, using the rat model of experimental autoimmune uveitis, which has clinical and histological features of pan uveitis in man, we evaluated the immunoregulatory function of circulating exosomes. Methods Experimental autoimmune uveitis was induced in Lewis rats either immunised with interphotoreceptor retinoid‐binding protein R16 peptides or injected with activated R16‐specific T cells. The disease incidence and severity were examined by indirect fundoscopy and flow cytometry. Circulating exosomes were isolated from peripheral blood of naïve and Day 14 R16 immunised Lewis rats. The effect of exosomes on specific T cells was evaluated by R16‐specific T cell proliferation, cytokine production and recurrent uveitis induction. Results Circulating exosomes derived from active immunised uveitis rats selectively inhibited immune responses of R16‐specific T cells in vitro. Vaccination of naïve rats with these exosomes reduced the incidence of recurrent uveitis in an antigen‐specific manner. Antigen‐specific uveitogenic T cells reduced IFN‐γ production and increased IL‐10 after vaccination. Conclusions Circulating exosomes in autoimmune uveitis have the potential to be a novel treatment for recurrent autoimmune uveitis.

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Circulating Exosomes Control CD4+ T Cell Immunometabolic Functions via the Transfer of miR-142 as a Novel Mediator in Myocarditis

Cited by 26 publications

References 64 publications

The role of non-coding RNAs in myocarditis: a narrative review

The role of non-coding RNAs in myocarditis: a narrative review

Increased Methyl-CpG-Binding Domain Protein 2 Promotes Cigarette Smoke-Induced Pulmonary Hypertension

Vaccination with circulating exosomes in autoimmune uveitis prevents recurrent intraocular inflammation

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