Myeloid resident cells in the islets of Langerhans are key players in presentation of islet antigens and islet trophic function: identification of their phenotype and ontogeny (P5232)

Abstract

Abstract The entry of autoreactive T cells to their target organ is important in autoimmunity since this initiates the inflammatory process. Islets of Langerhans contain a monocyte/macrophage-derived cell with important features and properties. This islet myeloid cell plays a central role in the interaction with diabetogenic T cells. We have studied in-depth the phenotype of the islet myeloid cells in the NOD and non-diabetic mouse strains and find 2 myeloid subsets: one subset (~85%), expressing MHC-II, CD11c, CD11b, F4/80 and LysM; and a minor subset, (~15%) expressing MHC-II, CD11c, CD11b, CD103, BTLA and LysM. Islet myeloid cells are stable in numbers and decrease 30% 7 days after whole body irradiation. Studies testing eGFP bone marrow transplantation has shown that islet myeloid cells can be replaced as early as 2 weeks post-transplant. Finally, we consider that in addition to their role of antigen presentation, the islet myeloid cell has a different and perhaps a more important role in islet physiology, which is to maintain the health of the islet. When a genetic mutation affects the presence of myeloid cells in islets (CSF-1-deficient mice), islets are reduced in size and show an altered glucose homeostasis. Our findings highlight the importance of the islet myeloid cell as central in presentation of islet antigen and trophic function of the islet. Their phenotype, ontogeny and trophic identification, will bring insights into diagnostics and point of interventions in diabetes.