As PMN-MDSCs were also increased in male CCRK TG mice under HFHC diet (Supplementary Fig. 4c), our data suggest that the obesity-triggered AR/CCRK signaling may establish an immunosuppressive barrier through induction of MDSC expansion and recruitment via NF-κB/IL-627 and mTORC1/G-CSF42 pathways, respectively. Here, AR is linked to obesity due to melanocortin 4 receptor deficiency.