Interleukin‐7‐dependent nonclassical monocytes and CD40 expression are affected in children with type 1 diabetes

Abstract

Abstract The important role of IL‐7 in the generation of self‐reactive T‐cells in autoimmune diseases is well established. Recent studies on autoimmunity‐associated genetic polymorphisms indicated that differential IL‐7 receptor (IL‐7R) expression of monocytes may play a role in the underlying pathogenesis. The relevance of IL‐7‐mediated monocyte functions in type 1 diabetes remains elusive. In the present study, we characterized monocyte phenotype and IL‐7‐mediated effects in children with type 1 diabetes and healthy controls with multicolor flow cytometry and t‐distributed Stochastic Neighbor‐Embedded (t‐SNE)‐analyses. IL‐7R expression of monocytes rapidly increased in vitro and was boosted through LPS. In the presence of IL‐7, we detected lower monocyte IL‐7R expression in type 1 diabetes patients as compared to healthy controls. This difference was most evident for the subset of nonclassical monocytes, which increased after IL‐7 stimulation. t‐SNE analyses revealed IL‐7‐dependent differences in monocyte subset distribution and expression of activation and maturation markers (i.e., HLA‐DR, CD80, CD86, CD40). Notably, monocyte CD40 expression increased considerably by IL‐7 and CD40/IL‐7R co‐expression differed between patients and controls. This study shows the unique effects of IL‐7 on monocyte phenotype and functions. Lower IL‐7R expression on IL‐7‐induced CD40 high monocytes and impaired IL‐7 response characterize monocytes from patients with type 1 diabetes.