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Clin Rev Allergy Immunol. 2014 Oct;47(2):174-92. doi: 10.1007/s12016-014-8422-2.

Molecular mechanisms in autoimmune type 1 diabetes: a critical review.

Author information

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.

Erratum in

  • Clin Rev Allergy Immunol. 2014 Oct;47(2):258.

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.

PMID:
24752371
DOI:
10.1007/s12016-014-8422-2
[Indexed for MEDLINE]

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