In all species, islets of Langerhans contain myeloid cells distributed among the endocrine cells. In the mouse, the species where most studies have been carried out, the myeloid cells are mostly represented by typical macrophages (reviewed in [
1]). Early studies that identified myeloid cells in islets claimed that they were likely to be ‘passenger leucocytes’; of interest, such cells were a component of the allogeneic response to islet transplantation [
2,
3]. Recent investigations examining cell surface markers and gene transcriptomes have shown that the islet myeloid cells are typical macrophages that reside in the islets and are distinct from the dendritic lineage cells (DCs) [
4‐
6]. These islet macrophages are found from birth, replicate in the islets, and are minimally (if at all) replaced by blood monocytes [
4]. Lineage-tracing studies indicate that the islet macrophages are derived from definitive haematopoiesis, while, in contrast, those residing in the inter-acinar stroma are derived from yolk sac haematopoiesis [
4]. Islet macrophages are highly activated independent of any inflammation [
7]. They have an M1-like profile, distinct from the M2-like profile of the stromal macrophages [
4]. Recent reports have reviewed the new information on the biology of resident macrophages [
8‐
10]. In the islet, macrophages are in intimate contact with beta cells. Through this cell contact, the beta cell–macrophage ‘synapse’, the macrophages take up insulin-containing vesicles [
11]. In the context of autoimmune type 1 diabetes, these findings need to be taken into consideration. Autoimmune recognition of beta cell antigens, such as insulin, requires an intermediate cell bearing class II major histocompatibility complex (MHCII) proteins. The islet macrophages and DCs, some of which enter islets, are key cells in this process.
In order to further extend our knowledge on the behaviour of islet macrophages, in this study we carried out live imaging of explanted islets under physiological conditions (electronic supplementary material [ESM] Fig.
1) and conducted electron microscopy studies, all in non-diabetic mice. We also performed functional assays in NOD mice, in order to correlate the morphological findings with the response of autoreactive CD4
+ T cells to insulin peptides presented by the MHCII molecules of macrophages.