The Immunoreactive Platform of the Pancreatic Islets Influences the Development of Autoreactivity

Diabetes. 2019 Aug;68(8):1544-1551. doi: 10.2337/dbi18-0048.


Tissue homeostasis is maintained through a finely tuned balance between the immune system and the organ-resident cells. Disruption of this process not only results in organ dysfunction but also may trigger detrimental autoimmune responses. The islet of Langerhans consists of the insulin-producing β-cells essential for proper control of body metabolism, but less appreciated is that these cells naturally interact with the immune system, forming a platform by which the β-cell products are sensed, processed, and responded to by the local immune cells, particularly the islet-resident macrophages. Although its physiological outcomes are not completely understood, this immunoreactive platform is crucial for precipitating islet autoreactivity in individuals carrying genetic risks, leading to the development of type 1 diabetes. In this Perspective, we summarize recent studies that examine the cross talk between the β-cells and various immune components, with a primary focus on discussing how antigenic information generated during normal β-cell catabolism can be delivered to the resident macrophage and further recognized by the adaptive CD4 T-cell system, a critical step to initiate autoimmune diabetes. The core nature of the islet immune platform can be extrapolated to other endocrine tissues and may represent a common mechanism underlying the development of autoimmune syndromes influencing multiple endocrine organs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / metabolism
  • Diabetes Mellitus, Type 1 / metabolism*
  • Female
  • Humans
  • Insulin / metabolism
  • Insulin-Secreting Cells / metabolism*
  • Islets of Langerhans / metabolism*
  • Macrophages / metabolism
  • Male
  • Mice
  • Mice, Inbred NOD
  • T-Lymphocytes / metabolism
  • Thymus Gland / metabolism


  • Insulin