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Current Diabetes Reports
Published in: Current Diabetes Reports 12/2017

01-12-2017 | Pathogenesis of Type 1 Diabetes (A Pugliese, Section Editor)

Autoimmune Responses to Exosomes and Candidate Antigens Contribute to Type 1 Diabetes in Non-Obese Diabetic Mice

Authors: Yang D. Dai, Huiming Sheng, Peter Dias, M. Jubayer Rahman, Roman Bashratyan, Danielle Regn, Kristi Marquardt

Published in: Current Diabetes Reports | Issue 12/2017

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Abstract

Purpose of Review

The initial autoimmune trigger of type 1 diabetes (T1D) remains unclear. In non-obese diabetic (NOD) mice, islet inflammation starts early in life, suggesting the presence of an endogenous trigger for the spontaneous autoimmune response in this T1D mouse model. In this review, we argue that abnormal release of exosomes might be the trigger of the early inflammatory and autoimmune responses in the islets.

Recent Findings

Exosomes are nano-sized membrane complexes that are secreted by cells following fusion of late endosomes and/or multivesicular bodies with the plasma membrane. They are known extracellular messengers, communicating among neighboring cells via transporting large molecules from parent cells to recipient cells. Recent evidence demonstrates that these extracellular vesicles can modulate immune responses. It has been shown that insulinoma and islet mesenchymal stem cell-released exosomes are potent immune stimuli that can induce autoreactive B and T cells. Searching for candidate antigens in the exosomes identified endogenous retrovirus (ERV) Env and Gag antigens, which are homologous to an endogenous murine leukemia retrovirus. Autoantibodies and autoreactive T cells spontaneously developed in NOD mice can react to these retroviral antigens. More importantly, expression of the retroviral antigens in the islet mesenchymal stem cells is associated with disease susceptibility, and the expression is restricted to T1D-susceptible but not resistant mouse strains.

Summary

Exosomes are novel autoimmune targets, carrying autoantigens that can stimulate innate and adaptive immune responses. An abnormal or excess release of exosomes, particularly those ones containing endogenous retroviral antigens might be responsible for triggering tissue-specific inflammatory and autoimmune responses.
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Metadata
Title
Autoimmune Responses to Exosomes and Candidate Antigens Contribute to Type 1 Diabetes in Non-Obese Diabetic Mice
Authors
Yang D. Dai
Huiming Sheng
Peter Dias
M. Jubayer Rahman
Roman Bashratyan
Danielle Regn
Kristi Marquardt
Publication date
01-12-2017
Publisher
Springer US
Published in
Current Diabetes Reports / Issue 12/2017
Print ISSN: 1534-4827
Electronic ISSN: 1539-0829
DOI
https://doi.org/10.1007/s11892-017-0962-4

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