Immunomodulatory Effect of Serum Exosomes From Crohn Disease on Macrophages via Let-7b-5p/TLR4 Signaling

作者：Lingqi Gong, Jintao Xiao, Jun Yi, Junbo Xiao, Fanggen Lu, Xiaowei Liu · 发表于：Inflammatory Bowel Diseases · 年份：2021 · DOI：10.1093/ibd/izab132 · 被引用次数：34 · 研究领域：Extracellular vesicles in disease、Inflammatory Bowel Disease、Immune cells in cancer

BACKGROUND: Exosomes are extensively reported to be strongly associated with many immunologic diseases, including Crohn disease (CD). Meanwhile, the dysfunction of macrophage activation has been proposed to be critical for the pathogenesis of CD. However, it is an unsettled issue whether serum exosomes from CD could activate macrophages and participate in its pathogenesis. Our study intended to clarify the role of CD-derived exosomes on macrophages to elucidate a novel mechanism and possible diagnostic and therapeutic strategies. METHODS: Serum exosomes were isolated and identified. Functional assays in vitro were performed on Raw264.7 macrophages, followed by exosomal microRNA (miRNA) profiling and bioinformatics analyses via high-throughput sequencing. In animal experiments, exosomes were intraperitoneally injected into dextran sulfate sodium-induced colitis. RESULTS: In vitro CD-derived exosomes induced proinflammatory cytokine expression and increased macrophage counts. Meanwhile, the intervention of exosomes from CD with epithelial cells led to increased permeability of the intestinal epithelial barrier. In vivo, CD-derived exosomes could circulate into the intestinal mucosa and significantly aggravate colitis. Furthermore, CD changed the miRNA profile of exosomes and further analysis revealed a differential expression of let-7b-5p. Mechanistically, the let-7b-5p/TLR4 pathway was recognized as a potential contributor to macrophage activation and inflammatory response. Fu...