Chapter

The Islets of Langerhans

Volume 654 of the series Advances in Experimental Medicine and Biology pp 537-583

Date:

Immunology of β-Cell Destruction

  • Daria La TorreAffiliated withLund University, CRC, Department of Clinical Sciences, University Hospital MAS Email author 
  • , Åke LernmarkAffiliated withLund University, CRC, Department of Clinical Sciences, University Hospital MAS

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Abstract

The pancreatic islet β-cells are the target for an autoimmune process that eventually results in an inability to control blood glucose due to the lack of insulin. The different steps that eventually lead to the complete loss of the β-cells are reviewed to include the very first step of a triggering event that initiates the development of β-cell autoimmunity to the last step of appearance of islet-cell autoantibodies, which may mark that insulitis is about to form. The observations that the initial β-cell destruction by virus or other environmental factors triggers islet autoimmunity not in the islets but in the draining pancreatic lymph nodes are reviewed along with possible basic mechanisms of loss of tolerance to islet autoantigens. Once islet autoimmunity is established the question is how β-cells are progressively killed by autoreactive lymphocytes which eventually results in chronic insulitis. Many of these series of events have been dissected in spontaneously diabetic mice or rats, but controlled clinical trials have shown that rodent observations are not always translated into mechanisms in humans. Attempts are therefore needed to clarify the step 1 triggering mechanisms and the step to chronic autoimmune insulitis to develop evidence-based treatment approaches to prevent type 1 diabetes.

Keywords

Islet autoimmunity Autoantigens Prediction Prevention Insulitis Islet autoantibodies CD4+ T cells CD8+ T cells T regulatory cells Antigen-presenting cells Dendritic cells