Insulinoma-released exosomes or microparticles are immunostimulatory and can activate autoreactive T cells spontaneously developed in nonobese diabetic mice

Sheng, Huiming, Hassanali, Saleena, Nugent, Courtney, Wen, Li, Hamilton-Williams, Emma, Dias, Peter and Dai, Yang D. (2011) Insulinoma-released exosomes or microparticles are immunostimulatory and can activate autoreactive T cells spontaneously developed in nonobese diabetic mice. Journal of Immunology, 187 4: 1591-1600. doi:10.4049/jimmunol.1100231


Author Sheng, Huiming
Hassanali, Saleena
Nugent, Courtney
Wen, Li
Hamilton-Williams, Emma
Dias, Peter
Dai, Yang D.
Title Insulinoma-released exosomes or microparticles are immunostimulatory and can activate autoreactive T cells spontaneously developed in nonobese diabetic mice
Journal name Journal of Immunology   Check publisher's open access policy
ISSN 0022-1767
1550-6606
Publication date 2011-08
Sub-type Article (original research)
DOI 10.4049/jimmunol.1100231
Volume 187
Issue 4
Start page 1591
End page 1600
Total pages 10
Place of publication Bethesda, MD, United States
Publisher American Association of Immunologists
Collection year 2012
Language eng
Abstract 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.
Keyword Glutamic-acid decarboxylase
Nod mice
Immune-responses
Membrane-vesicles
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
UQ Diamantina Institute - Open Access Collection
UQ Diamantina Institute Publications
 
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