Origins, recruitment, and regulation of CD11c+ cells in inflamed islets of autoimmune diabetes mice

CD11c + cells increase greatly with islet inflammation in non-obese diabetic mice and contribute to autoimmune destruction of pancreatic beta cells. In this study, we investigated their origin and mechanism of recruitment. CD11c + cells in inflamed islets resembled classical dendritic cells (DC) based on their transcriptional profile. However, the majority of these cells were not from the Zbtb46-dependent DC lineage. Instead, monocyte precursors could give rise to CD11c + cells in inflamed islets. Chemokines Ccl5 and Ccl8 were persistently elevated in inflamed islets and the influx of CD11c + cells was partially dependent on their receptor Ccr5. Treatment with islet antigen-specific regulatory T cells (Tregs) led to a marked decrease of Ccl5 and Ccl8 and a reduction of monocyte recruitment. These results implicate a monocytic origin of CD11c + cells in inflamed islets and suggest that therapeutic Tregs directly or indirectly regulate their influx by altering the chemotactic milieu in the islets.