Islet CD11c+ cells: Gatekeepers, Instigators, and Peacekeepers

Pancreatic islets contain resident myeloid cells that include macrophages and dendritic cells, with additional monocyte recruitment following autoimmune infiltration. These CD11c-expressing myeloid populations have diverse roles in modulating the T cell response in the islets over the course of islet infiltration and destruction. Data will be presented showing that islet CD11c⁺ cells are critical gatekeepers for lymphocyte entry into the pancreatic islets. Additionally, a subset of CD11c⁺ cells in islets with mild insulitis serve as antigen presenting cells that drive restimulation and pathogenesis of autoreactive T cells. However, as insulitis progresses, infiltrating CD11c⁺ cells drive a tolerance checkpoint that functions in the islets. While the functions of CD11c⁺ cells in the islets are varied, the mechanisms by which they modulate the autoreactive T cell response in the islets may be novel targets for disrupting the ongoing autoimmune response.