Further support for the hypothesis that persistent, hyper-expanded Tregs found in JIA SF are auto-reactive is provided by a recent study performed in mice with type 1 diabetes, where Tregs with a high degree of self-reactivity were found to be expanding locally in affected pancreatic islets and displayed a specific profile with elevated levels of GITR, CTLA-4, ICOS, and Ki67, very similar to our observations (Sprouse et al., 2018). This evidence concerns the gene ICOS and type 1 diabetes mellitus.