Our data suggest that increased tissue CCL5 expression is crucial for increasing CD11b+Ly6G−Ly6Chi pro-inflammatory M-MDSCs and suppressing CD11b+Ly6G−Ly6Clow reparative M-MDSCs, which may be associated with M1-M2 trans-differentiation and the development of obesity-induced adipose tissue inflammation through CCR5 receptor, which may contribute to the microenvironment that may foster the accumulation of these cells and serve as a feedback mechanism to curb the development of inflammation. Here, CCL5 is linked to obesity due to melanocortin 4 receptor deficiency.