دورية أكاديمية
أعرض في EDS

CD11c+ myeloid cell exosomes reduce intestinal inflammation during colitis.

التفاصيل البيبلوغرافية
العنوان: CD11c+ myeloid cell exosomes reduce intestinal inflammation during colitis.
المؤلفون: Bauer KM; Department of Pathology, Division of Microbiology and Immunology, University of Utah, Salt Lake City, Utah, USA., Nelson MC; Department of Pathology, Division of Microbiology and Immunology, University of Utah, Salt Lake City, Utah, USA., Tang WW; Department of Pathology, Division of Microbiology and Immunology, University of Utah, Salt Lake City, Utah, USA., Chiaro TR; Department of Pathology, Division of Microbiology and Immunology, University of Utah, Salt Lake City, Utah, USA., Brown DG; Department of Pathology, Division of Microbiology and Immunology, University of Utah, Salt Lake City, Utah, USA., Ghazaryan A; Department of Pathology, Division of Microbiology and Immunology, University of Utah, Salt Lake City, Utah, USA., Lee SH; Department of Pathology, Division of Microbiology and Immunology, University of Utah, Salt Lake City, Utah, USA., Weis AM; Department of Pathology, Division of Microbiology and Immunology, University of Utah, Salt Lake City, Utah, USA., Hill JH; Department of Pathology, Division of Microbiology and Immunology, University of Utah, Salt Lake City, Utah, USA., Klag KA; Department of Pathology, Division of Microbiology and Immunology, University of Utah, Salt Lake City, Utah, USA., Tran VB; Department of Pathology, Division of Microbiology and Immunology, University of Utah, Salt Lake City, Utah, USA., Thompson JW; Department of Pathology, Division of Microbiology and Immunology, University of Utah, Salt Lake City, Utah, USA., Ramstead AG; Department of Pathology, Division of Microbiology and Immunology, University of Utah, Salt Lake City, Utah, USA., Monts JK; University of Utah Flow Cytometry Core, Salt Lake City, Utah, USA., Marvin JE; University of Utah Flow Cytometry Core, Salt Lake City, Utah, USA., Alexander M; Department of Pathology, Division of Microbiology and Immunology, University of Utah, Salt Lake City, Utah, USA., Voth WP; Department of Pathology, Division of Microbiology and Immunology, University of Utah, Salt Lake City, Utah, USA., Stephens WZ; Department of Pathology, Division of Microbiology and Immunology, University of Utah, Salt Lake City, Utah, USA., Ward DM; Department of Pathology, Division of Microbiology and Immunology, University of Utah, Salt Lake City, Utah, USA., Petrey AC; Department of Pathology, Division of Microbiology and Immunology, University of Utah, Salt Lake City, Utah, USA.; Department of Internal Medicine, Division of Gastroenterology, and., Round JL; Department of Pathology, Division of Microbiology and Immunology, University of Utah, Salt Lake City, Utah, USA.; Hunstman Cancer Institute, University of Utah, Salt Lake City, Utah, USA., O'Connell RM; Department of Pathology, Division of Microbiology and Immunology, University of Utah, Salt Lake City, Utah, USA.; Hunstman Cancer Institute, University of Utah, Salt Lake City, Utah, USA.
المصدر: JCI insight [JCI Insight] 2022 Oct 10; Vol. 7 (19). Date of Electronic Publication: 2022 Oct 10.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 101676073 Publication Model: Electronic Cited Medium: Internet ISSN: 2379-3708 (Electronic) Linking ISSN: 23793708 NLM ISO Abbreviation: JCI Insight Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Ann Arbor, Michigan : American Society for Clinical Investigation, [2016]-
مواضيع طبية MeSH: CD11 Antigens*/genetics , CD11 Antigens*/immunology , Colitis*/genetics , Colitis*/immunology , Exosomes*/genetics , Exosomes*/immunology , Inflammation*/genetics , Inflammation*/immunology , Myeloid Cells*/immunology, Animals ; Inflammatory Bowel Diseases/immunology ; Intestines/immunology ; Lipids ; Mammals/genetics ; Mammals/immunology ; Mice ; MicroRNAs/immunology ; Monomeric GTP-Binding Proteins/immunology ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology ; TNF Receptor-Associated Factor 6/immunology
مستخلص: 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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معلومات مُعتمدة: F30 DK127846 United States DK NIDDK NIH HHS; F30 CA260977 United States CA NCI NIH HHS; T32 AI138945 United States AI NIAID NIH HHS; S10 OD026959 United States OD NIH HHS; T32 DK091317 United States DK NIDDK NIH HHS; R01 AI123106 United States AI NIAID NIH HHS; T32 HG008962 United States HG NHGRI NIH HHS
فهرسة مساهمة: Keywords: Cell Biology; Immunology; Inflammatory bowel disease; Noncoding RNAs
المشرفين على المادة: 0 (CD11 Antigens)
0 (Lipids)
0 (MicroRNAs)
0 (NLR Family, Pyrin Domain-Containing 3 Protein)
0 (TNF Receptor-Associated Factor 6)
EC 3.6.5.2 (Monomeric GTP-Binding Proteins)
تواريخ الأحداث: Date Created: 20221010 Date Completed: 20221011 Latest Revision: 20240607
رمز التحديث: 20240607
مُعرف محوري في PubMed: PMC9675566
DOI: 10.1172/jci.insight.159469
PMID: 36214220
قاعدة البيانات: MEDLINE
الوصف
تدمد:2379-3708
DOI:10.1172/jci.insight.159469