Learning from the reprogramming of Treg effector molecules from the transcriptome analysis, we identified that the splenic Tregs in hyperlipidemia tend to exert their functions through secreting IL-10, upregulating immune inhibitory checkpoint receptors to abrogate effector T cell functions, and executing cytotoxic effects directly via granzyme B. Clearly, we have verified — with flow cytometry — the upregulation of CTLA-4, TIGIT, and PD-1 in splenic Tregs and observed a higher IL-10 generation than WT Tregs. Here, GZMB is linked to hyperlipidemia.