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Molecular Mechanisms in Autoimmune Type 1 Diabetes: a Critical Review

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An Erratum to this article was published on 30 May 2014

Abstract

Autoimmune type 1 diabetes is characterized by selective destruction of insulin-secreting beta cells in the pancreas of genetically susceptible individuals. The mechanisms underlying the development of type 1 diabetes are not fully understood. However, a widely accepted point is that type 1 diabetes is caused by a combination of genetic and environmental factors. Although most type 1 diabetes patients do not have a family history, genetic susceptibility does play a vital role in beta cell autoimmunity and destruction. Human leukocyte antigen (HLA) regions are the strongest genetic determinants, which can contribute 40–50 % of the genetic risk to type 1 diabetes. Other genes, including INS also contribute to disease risk. The mechanisms of the susceptible genes in type 1 diabetes may relate to their respective roles in antigen presentation, beta cell autoimmunity, immune tolerance, and autoreactive T cell response. Environmental susceptibility factors also contribute to the risk of developing type 1 diabetes. From an epigenetic standpoint, the pathologic mechanisms involved in the development of type 1 diabetes may include DNA methylation, histone modification, microRNA, and molecular mimicry. These mechanisms may act through regulating of gene expression, thereby affecting the immune system response toward islet beta cells. One of the characteristics of type 1 diabetes is the recognition of islet autoantigens by autoreactive CD4+ and CD8+ T cells and autoantibodies. Autoantibodies against islet autoantigens are involved in autoantigen processing and presentation by HLA molecules. This review will mainly focus on the molecular mechanism by which genetic, epigenetic, and environmental factors contribute to the risk of type 1 diabetes.

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Acknowledgments

We would like to thank Dr. Eric Gershwin and Qianjin Lu for their advice and proofreading of the manuscript. This work was supported by the National Natural Science Foundation of China (Grant No. 81170725), the European Foundation for the Study of Diabetes (Grant No. EFSD/CDS/Lilly-2010), Hunan Provincial Natural Science Foundation of China (11JJ7005), Program for Changjiang Scholars and Innovative Research Team in University (IRT1195) and the National Key Technology R&D program (2012BAI02B04).

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Authors and Affiliations

  1. Diabetes Center, 2nd Xiangya Hospital, and Institute of Metabolism and Endocrinology, Key Laboratory of Diabetes Immunology, Ministry of Education, Central South University, Changsha, Hunan, 410011, China

    Zhiguo Xie & Zhiguang Zhou

  2. Division of Allergy and Immunology, Thomas Jefferson University, Nemours/A.I. duPont Hospital for Children, 1600 Rockland Road, Wilmington, DE, 19803, USA

    Christopher Chang

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  1. Zhiguo Xie
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  2. Christopher Chang
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  3. Zhiguang Zhou
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Correspondence to Christopher Chang.

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Xie, Z., Chang, C. & Zhou, Z. Molecular Mechanisms in Autoimmune Type 1 Diabetes: a Critical Review. Clinic Rev Allerg Immunol 47, 174–192 (2014). https://doi.org/10.1007/s12016-014-8422-2

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