Abstract
The classical view of type 1 diabetes assumes that the autoimmune mediated targeting of insulin producing ß-cells is caused by an error of the immune system. Malfunction and stress of beta cells added the target tissue at the center of action. The innate immune system, and in particular islet-resident cells of the myeloid lineage, could function as a link between stressed ß-cells and activation and recognition by the adaptive immune system. We survey the role of islet-resident macrophages and dendritic cells in healthy islet homeostasis and pathophysiology of T1D. Knowledge of islet-resident antigen presenting cells in rodents is substantial, but quite scarce in humans, in particular regarding dendritic cells. Differences in blood between healthy and diseased individuals were reported, but it remains elusive to what extend these contribute to T1D onset. Increasing our understanding of the interaction between ß-cells and innate immune cells may provide new insights into disease initiation and development that could ultimately point to future treatment options. Here we review current knowledge of islet-resident macrophages and dendritic cells, place these in context of current clinical trials, and guide future research.
Highlights
Type 1 diabetes is characterized by the loss of insulin-producing ß-cells in pancreatic islets of Langerhans leading to insulin shortage
We recently showed that tolDCs generated from T1D patients’ blood induce immune tolerance indifferently from those from healthy individuals, proving that they still possess their immune-regulatory capacity [47]
Where is ‘Bigfoot’, the dendritic cell in human islets? While mouse studies suggest that the myeloid compartment in islets is up to 98% consisting of macrophages, the rare studies on human islets pointed that 50% of leukocytes at best were macrophages, while the other 50% was ignored
Summary
Type 1 diabetes is characterized by the loss of insulin-producing ß-cells in pancreatic islets of Langerhans leading to insulin shortage. Given that APCs play a crucial role in T1D onset by connecting ß-cells to the adaptive immune system, it is worth to assess differences in APCs between healthy individuals and T1D patients. T-cells from macrophagedepleted NOD mice were unable to induce diabetes upon transfer into NOD.scid mice [59,60,61] Beside their function as APCs, macrophages play a critical role in tissue development and remodeling (Figure 1), where they promote proliferation of ß-cells by creating a favorable microenvironment and upregulation of SMAD7 [62,63,64,65]. This strategy will be tested for its capacity to delay disease progression and preserve endogenous betacell function
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
