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Exosomes released by islet-derived mesenchymal stem cells trigger autoimmune responses in NOD mice

Academic Article
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Overview

authors

  • Rahman, M. J.
  • Regn, D.
  • Bashratyan, R.
  • Dai, Yang D.

publication date

  • 2014

journal

  • Diabetes  Journal

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 infiltration 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.

subject areas

  • Animals
  • Autoimmunity
  • Cells, Cultured
  • Exosomes
  • Immunologic Memory
  • Interferon-gamma
  • Intracellular Signaling Peptides and Proteins
  • Islets of Langerhans
  • Lymphocytes
  • Mesenchymal Stem Cells
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred NOD
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Identity

PubMed Central ID

  • PMC3931393

International Standard Serial Number (ISSN)

  • 0012-1797

Digital Object Identifier (DOI)

  • 10.2337/db13-0859

PubMed ID

  • 24170696
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Additional Document Info

start page

  • 1008

end page

  • 1020

volume

  • 63

issue

  • 3

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