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Review
. 2016 Dec;43:54-59.
doi: 10.1016/j.coi.2016.09.004. Epub 2016 Oct 4.

Macrophages and Dendritic Cells in Islets of Langerhans in Diabetic Autoimmunity: A Lesson on Cell Interactions in a Mini-Organ

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Free PMC article
Review

Macrophages and Dendritic Cells in Islets of Langerhans in Diabetic Autoimmunity: A Lesson on Cell Interactions in a Mini-Organ

Javier A Carrero et al. Curr Opin Immunol. .
Free PMC article

Abstract

Islets of Langerhans of all species harbor a small number of resident macrophages. These macrophages are found since birth, do not exchange with blood monocytes, and are maintained by a low level of replication. Under steady state conditions, the islet macrophages are in an activated state. Islet macrophages have an important homeostatic role in islet physiology. At the start of the autoimmune process in the NOD mouse, a small number of CD103+ dendritic cells (DC) are found at about the same time that CD4+ T cells also appear in islets. In the absence of the CD103+ DC in the Batf3 deficient mice, autoimmunity never develops. We discuss the interactions among the two phagocytes and beta cells that result in autoimmune diabetes in NOD mice.

Figures

Figure 1
Figure 1
An electron micrograph of an islet from an 8 week-old NOD mouse. The image shows a phagocyte wrapped around a blood vessel. Note a dense core granule inside a phagocytic vesicle. Islet phagocytes contain about 10 granules per cell. Unpublished micrograph.
Figure 2
Figure 2
The graph summarizes the main points made in the review. Islets of all species contain macrophages that are in true symbiosis with beta cells. In NOD mice at the start of the autoimmune process, the CD103+ DC join the macrophages in the islets. Both capture dense core granules and present to insulin-reactive CD4 T cells. However, it is the CD103+DC that is essential to move the autoimmune process forward. At the same time CD4 T cells to insulin appear in islets together with a new gene signature. The process readily extends to the pancreatic node where the autoimmune process is amplified.

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