Bone marrow transplantation and RNAseq analysis of Gpr21^−/− monocytes reveals reduced migratory function and downregulation of inflammatory genes

Immune cell infiltration into tissues produces chronic low-grade inflammation leading to obesity-induced insulin resistance . Insight into this mechanistic link has revealed activation of various receptors including the orphan G protein-coupled receptor, GPR21 .GPR21 is widely expressed throughout the body, and on immune cells including monocytes and macrophages . Transplantation of bone marrow from wild-type or Gpr21 animals into irradiated wild-type animals fed normal chow (13.5% fat), or high fat diet (HFD; 60% fat) for 27 weeks, revealed no improvement in glucose homeostasis, but an improvement in insulin sensitivity and a decrease in immune cell infiltration into eWAT. Furthermore, a decrease in the migratory ability of isolated CD11b bone marrow monocytes from Gpr21 mice compared to wild-type in response to monocyte chemo attractant protein-1 (MCP-1) was observed. These data were confirmed using aPKH26 monocyte tracking study. RNAseq analysis of CD11b monocytes from Gpr21 mice revealed an overall significant effect on genes involved in inflammation and cell migration, including Il6, Ccl2, Cxcl2 and members of the TLR family, supporting the reduced functional response. Significant changes in genes involved in atherosclerosis was also observed, including Apoe and Nr4a1. These data indicate that GPR21 is involved in the chemotaxis of specific immune cells. Targeting this receptor may prove beneficial for the treatment of T2DM and its complications.