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Exosomes Released by Islet-Derived Mesenchymal Stem Cells Trigger Autoimmune Responses in NOD Mice

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 investig...

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Detalles Bibliográficos
Autores principales: Rahman, Muhammad Jubayer, Regn, Danielle, Bashratyan, Roman, Dai, Yang D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3931393/
https://www.ncbi.nlm.nih.gov/pubmed/24170696
http://dx.doi.org/10.2337/db13-0859
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author Rahman, Muhammad Jubayer
Regn, Danielle
Bashratyan, Roman
Dai, Yang D.
author_facet Rahman, Muhammad Jubayer
Regn, Danielle
Bashratyan, Roman
Dai, Yang D.
author_sort Rahman, Muhammad Jubayer
collection PubMed
description 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.
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spelling pubmed-39313932015-03-01 Exosomes Released by Islet-Derived Mesenchymal Stem Cells Trigger Autoimmune Responses in NOD Mice Rahman, Muhammad Jubayer Regn, Danielle Bashratyan, Roman Dai, Yang D. Diabetes Islet Studies 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. American Diabetes Association 2014-03 2014-02-13 /pmc/articles/PMC3931393/ /pubmed/24170696 http://dx.doi.org/10.2337/db13-0859 Text en © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Islet Studies
Rahman, Muhammad Jubayer
Regn, Danielle
Bashratyan, Roman
Dai, Yang D.
Exosomes Released by Islet-Derived Mesenchymal Stem Cells Trigger Autoimmune Responses in NOD Mice
title Exosomes Released by Islet-Derived Mesenchymal Stem Cells Trigger Autoimmune Responses in NOD Mice
title_full Exosomes Released by Islet-Derived Mesenchymal Stem Cells Trigger Autoimmune Responses in NOD Mice
title_fullStr Exosomes Released by Islet-Derived Mesenchymal Stem Cells Trigger Autoimmune Responses in NOD Mice
title_full_unstemmed Exosomes Released by Islet-Derived Mesenchymal Stem Cells Trigger Autoimmune Responses in NOD Mice
title_short Exosomes Released by Islet-Derived Mesenchymal Stem Cells Trigger Autoimmune Responses in NOD Mice
title_sort exosomes released by islet-derived mesenchymal stem cells trigger autoimmune responses in nod mice
topic Islet Studies
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3931393/
https://www.ncbi.nlm.nih.gov/pubmed/24170696
http://dx.doi.org/10.2337/db13-0859
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