| Insulinoma-Released Exosomes or Microparticles Are Immunostimulatory and Can Activate Autoreactive T Cells Spontaneously Developed in Nonobese Diabetes Mice. | |
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MedLine Citation:
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PMID: 21734072 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Exosomes (EXO) are secreted intracellular microparticles that can trigger inflammation and induce Ag-specific immune responses. To test possible roles of EXO in autoimmunity, we isolated small microparticles, mainly EXO, from mouse insulinoma and examined their activities to stimulate the autoimmune responses in NOD mice, a model for human type 1 diabetes. We demonstrate that the EXO contains strong innate stimuli and expresses candidate diabetes autoantigens. They can induce secretion of inflammatory cytokines through a MyD88-dependent pathway, and activate purified APC and result in T cell proliferation. To address whether EXO or the secreted microparticles are possible autoimmune targets causing islet-specific inflammation, we monitored the T cell responses spontaneously developed in prediabetic NOD mice for their reactivity to the EXO, and compared this reactivity between diabetes-susceptible and -resistant congenic mouse strains. We found that older NOD females, which have advanced islet destruction, accumulated more EXO-reactive, IFN-γ-producing lymphocytes than younger females or age-matched males, and that pancreatic lymph nodes from the prediabetic NOD, but not from the resistant mice, were also enriched with EXO-reactive Th1 cells. In vivo, immunization with the EXO accelerates insulitis development in nonobese diabetes-resistant mice. Thus, EXO or small microparticles can be recognized by the diabetes-associated autoreactive T cells, supporting that EXO might be a possible autoimmune target and/or insulitis trigger in NOD or congenic mouse strains. |
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Authors:
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Huiming Sheng; Saleema Hassanali; Courtney Nugent; Li Wen; Emma Hamilton-Williams; Peter Dias; Yang D Dai |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-7-6 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: - ISSN: 1550-6606 ISO Abbreviation: - Publication Date: 2011 Jul |
Date Detail:
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Created Date: 2011-7-7 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Division of Immune Regulation, Torrey Pines Institute for Molecular Studies, San Diego, CA 92121; |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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