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    Review of 'CD11c <sup>+</sup> myeloid cell exosomes reduce intestinal inflammation during colitis'

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    CD11c <sup>+</sup> myeloid cell exosomes reduce intestinal inflammation during colitisCrossref
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    CD11c + myeloid cell exosomes reduce intestinal inflammation during colitis

    Intercellular communication is critical for homeostasis in mammalian systems, including the gastrointestinal (GI) tract. Exosomes are nanoscale lipid extracellular vesicles that mediate communication between many cell types. Notably, the roles of immune cell exosomes in regulating GI homeostasis and inflammation are largely uncharacterized. By generating mouse strains deficient in cell-specific exosome production, we demonstrate deletion of the small GTPase Rab27A in CD11c + cells exacerbated murine colitis, which was reversible through administration of DC-derived exosomes. Profiling RNAs within colon exosomes revealed a distinct subset of miRNAs carried by colon- and DC-derived exosomes. Among antiinflammatory exosomal miRNAs, miR-146a was transferred from gut immune cells to myeloid and T cells through a Rab27-dependent mechanism, targeting Traf6 , IRAK-1 , and NLRP3 in macrophages. Further, we have identified a potentially novel mode of exosome-mediated DC and macrophage crosstalk that is capable of skewing gut macrophages toward an antiinflammatory phenotype. Assessing clinical samples, RAB27A , select miRNAs, and RNA-binding proteins that load exosomal miRNAs were dysregulated in ulcerative colitis patient samples, consistent with our preclinical mouse model findings. Together, our work reveals an exosome-mediated regulatory mechanism underlying gut inflammation and paves the way for potential use of miRNA-containing exosomes as a novel therapeutic for inflammatory bowel disease.
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      Review information

      10.14293/S2199-1006.1.SOR-UNCAT.A9675566.v1.RLWXHT
      This work has been published open access under Creative Commons Attribution License CC BY 4.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Conditions, terms of use and publishing policy can be found at www.scienceopen.com.

      noncoding rnas,cell biology,immunology,inflammatory bowel disease
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      The roles of extracellular vesicles/exosomes in gastrointestinal homeostasis and inflammation have not been extensively studies. Some antiinflammatory exosomal miRNAs were detected to transferr from immune cells to gastrointestinal lesion cells. Altogether, the results demostrated the potential of miRNA-containing exosomes to treat inflammatory bowel disease.

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