Critical contributions of protein cargos to the functions of macrophage-derived extracellular vesicles

Journal of Nanobiotechnology

Research

Xiao Cheng¹  Xinghui Sun¹  Jeffrey Price²  Amanda Ramer-Tait²  Chittibabu Guda³  Meng Niu³  Xingzhi Li⁴  Baolong Liu⁴  Jiujiu Yu⁴  Phuong Linh Nguyen⁴  Han Yu⁴  Huiren Wang⁴  Regis Moreau⁵  Sophie Alvarez⁶  Michael J. Naldrett⁶ 

[1] Department of Biochemistry, University of Nebraska-Lincoln, N158 Beadle Center, 68588-0665, Lincoln, NE, USA;Department of Food Science and Technology, University of Nebraska-Lincoln, 260 Food Innovation Center, 68588, Lincoln, NE, USA;Nebraska Food for Health Center, University of Nebraska-Lincoln, 115 Food Innovation Center, 68588, Lincoln, NE, USA;Department of Genetics, Cell Biology and Anatomy, Bioinformatics and Systems Biology Core, University of Nebraska Medical Center, 68198, Omaha, NE, USA;Department of Nutrition and Health Sciences, University of Nebraska-Lincoln, 230 Filley Hall, 68583, Lincoln, NE, USA;Department of Nutrition and Health Sciences, University of Nebraska-Lincoln, 316E Ruth Leverton Hall, 68583, Lincoln, NE, USA;Proteomics and Metabolomics Facility, Nebraska Center for Biotechnology, University of Nebraska-Lincoln, 68588, Lincoln, NE, USA;

关键词: Extracellular vesicles;    Exosomes;    M1 macrophages;    M2 macrophages;    Protein cargos;    Tight junction;    Colitis;   

DOI  :  10.1186/s12951-023-02105-9

 received in 2023-05-03, accepted in 2023-09-13,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundMacrophages are highly plastic innate immune cells that play key roles in host defense, tissue repair, and homeostasis maintenance. In response to divergent stimuli, macrophages rapidly alter their functions and manifest a wide polarization spectrum with two extremes: M1 or classical activation and M2 or alternative activation. Extracellular vesicles (EVs) secreted from differentially activated macrophages have been shown to have diverse functions, which are primarily attributed to their microRNA cargos. The role of protein cargos in these EVs remains largely unexplored. Therefore, in this study, we focused on the protein cargos in macrophage-derived EVs.ResultsNaïve murine bone marrow-derived macrophages were treated with lipopolysaccharide or interlukin-4 to induce M1 or M2 macrophages, respectively. The proteins of EVs and their parental macrophages were subjected to quantitative proteomics analyses, followed by bioinformatic analyses. The enriched proteins of M1-EVs were involved in proinflammatory pathways and those of M2-EVs were associated with immunomodulation and tissue remodeling. The signature proteins of EVs shared a limited subset of the proteins of their respective progenitor macrophages, but they covered many of the typical pathways and functions of their parental cells, suggesting their respective M1-like and M2-like phenotypes and functions. Experimental examination validated that protein cargos in M1- or M2-EVs induced M1 or M2 polarization, respectively. More importantly, proteins in M1-EVs promoted viability, proliferation, and activation of T lymphocytes, whereas proteins in M2-EVs potently protected the tight junction structure and barrier integrity of epithelial cells from disruption. Intravenous administration of M2-EVs in colitis mice led to their accumulation in the colon, alleviation of colonic inflammation, promotion of M2 macrophage polarization, and improvement of gut barrier functions. Protein cargos in M2-EVs played a key role in their protective function in colitis.ConclusionThis study has yielded a comprehensive unbiased dataset of protein cargos in macrophage-derived EVs, provided a systemic view of their potential functions, and highlighted the important engagement of protein cargos in the pathophysiological functions of these EVs.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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