Skeletal myotube-derived extracellular vesicles enhance itaconate production and attenuate inflammatory responses of macrophages

doi:10.3389/fimmu.2023.1099799

	Skeletal myotube-derived extracellular vesicles enhance itaconate production and attenuate inflammatory responses of macrophages
	Yamaguchi, Atomu 1; Maeshige, Noriaki 1; Yan, Jiawei2 ; Ma, Xiaoqi 1; Uemura, Mikiko 1; Matsuda, Mami 3; Nishimura, Yuya 3; Hasunuma, Tomohisa 3,4; Kondo, Hiroyo 5; Fujino, Hidemi 1; Yuan, Zhi-Min 6
	2023-03-02
发表期刊	FRONTIERS IN IMMUNOLOGY
ISSN	1664-3224
卷号	14
发表状态	已发表
DOI	10.3389/fimmu.2023.1099799
摘要	IntroductionMacrophages play an important role in the innate immunity. While macrophage inflammation is necessary for biological defense, it must be appropriately controlled. Extracellular vesicles (EVs) are small vesicles released from all types of cells and play a central role in intercellular communication. Skeletal muscle has been suggested to release anti-inflammatory factors, but the effect of myotube-derived EVs on macrophages is unknown. As an anti-inflammatory mechanism of macrophages, the immune responsive gene 1 (IRG1)-itaconate pathway is essential. In this study, we show that skeletal muscle-derived EVs suppress macrophage inflammatory responses, upregulating the IRG1-itaconate pathway. MethodsC2C12 myoblasts were differentiated into myotubes and EVs were extracted by ultracentrifugation. Skeletal myotube-derived EVs were administered to mouse bone marrow-derived macrophages, then lipopolysaccharide (LPS) stimulation was performed and inflammatory cytokine expression was measured by RT-qPCR. Metabolite abundance in macrophages after addition of EVs was measured by CE/MS, and IRG1 expression was measured by RT-PCR. Furthermore, RNA-seq analysis was performed on macrophages after EV treatment. ResultsEVs attenuated the expression of LPS-induced pro-inflammatory factors in macrophages. Itaconate abundance and IRG1 expression were significantly increased in the EV-treated group. RNA-seq analysis revealed activation of the PI3K-Akt and JAK-STAT pathways in macrophages after EV treatment. The most abundant miRNA in myotube EVs was miR-206-3p, followed by miR-378a-3p, miR-30d-5p, and miR-21a-5p. DiscussionSkeletal myotube EVs are supposed to increase the production of itaconate via upregulation of IRG1 expression and exhibited an anti-inflammatory effect in macrophages. This anti-inflammatory effect was suggested to involve the PI3K-Akt and JAK-STAT pathways. The miRNA profiles within EVs implied that miR-206-3p, miR-378a-3p, miR-30d-5p, and miR-21a-5p may be responsible for the anti-inflammatory effects of the EVs. In summary, in this study we showed that myotube-derived EVs prevent macrophage inflammatory responses by activating the IRG1-itaconate pathway.
关键词	extracellular vesicle skeletal muscle macrophage itaconate IRG1
URL	查看原文
收录类别	SCI
语种	英语
资助项目	JSPS KAKENH["17H04747","21H03852"]
WOS研究方向	Immunology
WOS类目	Immunology
WOS记录号	WOS:000950081000001
出版者	FRONTIERS MEDIA SA
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/287883
专题	生命科学与技术学院生命科学与技术学院_PI研究组_洪诗雅组
通讯作者	Maeshige, Noriaki; Fujino, Hidemi
作者单位	1.Kobe Univ, Grad Sch Hlth Sci, Dept Rehabil Sci, Kobe, Japan 2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 3.Kobe Univ, Grad Sch Sci Technol & Innovat, Kobe, Japan 4.Kobe Univ, Engn Biol Res Ctr, Kobe, Japan 5.Nagoya Womens Univ, Dept Food Sci & Nutr, Nagoya, Japan 6.Harvard Univ, TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA
推荐引用方式 GB/T 7714	Yamaguchi, Atomu,Maeshige, Noriaki,Yan, Jiawei,et al. Skeletal myotube-derived extracellular vesicles enhance itaconate production and attenuate inflammatory responses of macrophages[J]. FRONTIERS IN IMMUNOLOGY,2023,14.
APA	Yamaguchi, Atomu.,Maeshige, Noriaki.,Yan, Jiawei.,Ma, Xiaoqi.,Uemura, Mikiko.,...&Yuan, Zhi-Min.(2023).Skeletal myotube-derived extracellular vesicles enhance itaconate production and attenuate inflammatory responses of macrophages.FRONTIERS IN IMMUNOLOGY,14.
MLA	Yamaguchi, Atomu,et al."Skeletal myotube-derived extracellular vesicles enhance itaconate production and attenuate inflammatory responses of macrophages".FRONTIERS IN IMMUNOLOGY 14(2023).