Chemokines mediate leukocyte migration during immune responses. They can also affect cell migration during embryonic development, and Gerry Graham’s lab have previously shown that ACKR2, an atypical chemokine receptor expressed in the placenta, sequesters chemokines produced during the maternal immune response to prevent them from entering the embryo. Here, they focus on ACKR3, which scavenges the well-studied chemokine CXCL12. Immunofluorescence staining in murine and human placentas shows that ACKR3 is expressed specifically in the syncytiotrophoblasts, the epithelial cells of the placenta that form a barrier between the maternal and embryonic blood. CXCL12 is also present in these cells, and depletion of maternal ACKR3 in mice results in elevated levels of CXCL12 in the embryonic blood. ACKR3 knockout is perinatally lethal, so the authors use a known blocker of ACKR3 to reduce its activity in the mother. They find that blocking ACKR3 results in smaller, paler offspring that exhibit reduced levels of red blood cells, haematopoietic stem cells and B cells. When challenged by bacterial infection, the affected offspring are unable to mount proper inflammatory immune responses. Overall, this work suggests that ACKR3 expression in the placenta ensures proper haematopoiesis in the embryo by preventing maternal CXCL12 from entering the embryonic bloodstream.
