Phagocytosis by macrophages promotes pancreatic β cell mass reduction after parturition in mice

Abstract

Elucidating the mechanism(s) modulating appropriate tissue size is a critical biological issue. Pancreatic β cells increase during pregnancy via cellular proliferation, but how β cells promptly decrease to the original amount after parturition remains unclear. Herein, we demonstrate the role and mechanism of macrophage accumulation in this process. In the final stage of pregnancy, HTR1D signaling upregulates murine β cell CXCL10, thereby promoting macrophage accumulation in pancreatic islets via the CXCL10-CXCR3 axis. Blocking this mechanism by administering an HTR1D antagonist or the CXCR3 antibody and depleting islet macrophages inhibited postpartum β cell mass reduction. β cells engulfed by macrophages increased in postpartum islets, but Annexin V administration suppressed this engulfment and the postpartum β cell mass reduction, indicating the accumulated macrophages to phagocytose β cells. This mechanism contributes to both maintenance of appropriate β cell mass and glucose homeostasis promptly adapting to reduced systemic insulin demand after parturition.

Keywords: CXCL10; CXCR3; HTR1D; macrophages; pancreatic islets; phagocytosis; phosphatidylserine; pregnancy; serotonin; β cell mass.