{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:25:20Z","timestamp":1790691920181,"version":"4.1.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2017,11,1]],"date-time":"2017-11-01T00:00:00Z","timestamp":1509494400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Extracellular vesicles, including exosomes, have recently been implicated as novel mediators of immune cell communication in mammals. However, roles for endogenously produced exosomes in regulating immune cell functions in vivo are just beginning to be identified. In this article, we demonstrate that Rab27a and Rab27b double-knockout (Rab27DKO) mice that are deficient in exosome secretion have a chronic, low-grade inflammatory phenotype characterized by elevated inflammatory cytokines and myeloproliferation. Upon further investigation, we found that some of these phenotypes could be complemented by wild-type (WT) hematopoietic cells or administration of exosomes produced by GM-CSF\u2013expanded bone marrow cells. In addition, chronically inflamed Rab27DKO mice had a blunted response to bacterial LPS, resembling endotoxin tolerance. This defect was rescued by bone marrow exosomes from WT, but not miR-155\u2212\/\u2212, cells, suggesting that uptake of miR-155\u2013containing exosomes is important for a proper LPS response. Further, we found that SHIP1 and IRAK-M, direct targets of miR-155 that are known negative regulators of the LPS response, were elevated in Rab27DKO mice and decreased after treatment with WT, but not miR-155\u2212\/\u2212, exosomes. Together, our study finds that Rab27-dependent exosome production contributes to homeostasis within the hematopoietic system and appropriate responsiveness to inflammatory stimuli.<\/jats:p>","DOI":"10.4049\/jimmunol.1700904","type":"journal-article","created":{"date-parts":[[2017,10,5]],"date-time":"2017-10-05T00:40:16Z","timestamp":1507164016000},"page":"3559-3570","source":"Crossref","is-referenced-by-count":91,"title":["Rab27-Dependent Exosome Production Inhibits Chronic Inflammation and Enables Acute Responses to Inflammatory Stimuli"],"prefix":"10.1093","volume":"199","author":[{"given":"Margaret","family":"Alexander","sequence":"first","affiliation":[{"name":"Division of Microbiology and Immunology, Department of Pathology, University of Utah , Salt Lake City, UT 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew G","family":"Ramstead","sequence":"additional","affiliation":[{"name":"Division of Microbiology and Immunology, Department of Pathology, University of Utah , Salt Lake City, UT 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaylyn M","family":"Bauer","sequence":"additional","affiliation":[{"name":"Division of Microbiology and Immunology, Department of Pathology, University of Utah , Salt Lake City, UT 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soh-Hyun","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Microbiology and Immunology, Department of Pathology, University of Utah , Salt Lake City, UT 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marah C","family":"Runtsch","sequence":"additional","affiliation":[{"name":"Division of Microbiology and Immunology, Department of Pathology, University of Utah , Salt Lake City, UT 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jared","family":"Wallace","sequence":"additional","affiliation":[{"name":"Division of Microbiology and Immunology, Department of Pathology, University of Utah , Salt Lake City, UT 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas B","family":"Huffaker","sequence":"additional","affiliation":[{"name":"Division of Microbiology and Immunology, Department of Pathology, University of Utah , Salt Lake City, UT 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9841-1443","authenticated-orcid":false,"given":"Dane K","family":"Larsen","sequence":"additional","affiliation":[{"name":"Division of Microbiology and Immunology, Department of Pathology, University of Utah , Salt Lake City, UT 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8841-0797","authenticated-orcid":false,"given":"Tanya","family":"Tolmachova","sequence":"additional","affiliation":[{"name":"Molecular Medicine Section, National Heart and Lung Institute, Imperial College London , London SW7 2AZ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6404-4892","authenticated-orcid":false,"given":"Miguel C","family":"Seabra","sequence":"additional","affiliation":[{"name":"Molecular Medicine Section, National Heart and Lung Institute, Imperial College London , London SW7 2AZ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"June L","family":"Round","sequence":"additional","affiliation":[{"name":"Division of Microbiology and Immunology, Department of Pathology, University of Utah , Salt Lake City, UT 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane M","family":"Ward","sequence":"additional","affiliation":[{"name":"Division of Microbiology and Immunology, Department of Pathology, University of Utah , Salt Lake City, UT 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan M","family":"O\u2019Connell","sequence":"additional","affiliation":[{"name":"Division of Microbiology and Immunology, Department of Pathology, University of Utah , Salt Lake City, UT 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,11,15]]},"reference":[{"key":"2025030614524599300_r1","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.1172\/JCI200319451","article-title":"Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance","volume":"112","author":"Xu","year":"2003","journal-title":"J. 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