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- Title
Exosomes Released by Islet-Derived Mesenchymal Stem Cells Trigger Autoimmune Responses in NOD Mice.
- Authors
Muhammad Jubayer Rahman; Regn, Danielle; Bashratyan, Roman; Yang D. Dai
- Abstract
Exosomes (EXOs) are secreted, nano-sized membrane vesicles that contain potent immunostimulatory materials. We have recently demonstrated that insulinoma-released EXOs can stimulate the autoimmune responses in nonobese diabetic (NOD) mice, a spontaneous disease model for type 1 diabetes. To investigate whether primary islet cells can produce EXOs, we isolated cells from the islet of Langerhans of NOD mice and cultured them in vitro. Interestingly, cultured islets release fibroblast-like, fast-replicating cells that express mesenchymal stem cell (MSC) markers, including CD105 and stem-cell antigen-1. These islet MSC--like cells release highly immunostimulatory EXOs that could activate autoreactive B and T cells endogenously primed in NOD mice. Serum EXO levels and EXO-induced interferon-γ production were positively correlated with disease progression at the early prediabetic stage. Consistent with these observations, immunohistological analysis of pancreata showed that CD105+ cells are restricted to the peri-islet area in normal islets but penetrate into the β-cell area as lymphocyte in filtration occurs. Immunization with EXOs promoted expansion of transferred diabetogenic T cells and accelerated the effector T cell--mediated destruction of islets. Thus, EXOs could be the autoantigen carrier with potent adjuvant activities and may function as the autoimmune trigger in NOD mice.
- Subjects
EXOSOMES; VESICLES (Cytology); PEOPLE with diabetes; LABORATORY mice; T cells
- Publication
Diabetes, 2014, Vol 63, Issue 3, p1008
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db13-0859