Although the proportion of Tregs was similar between two groups (ESM Fig. 7b), it was noted that serum derived from diabetic individuals induced significantly higher levels of IFN-γ+FOXP3+ Tregs, and blockade of HMGB1 by the neutralising antibody remarkably reduced the induction of IFN-γ+FOXP3+ Tregs (Fig. 8d,e), supporting the theory that circulating HMGB1 impairs Treg stability in individuals with type 1 diabetes. Here, FOXP3 is linked to type 1 diabetes mellitus.