Xenophagocytosis blockade enhances interspecies chimerism - PubMed
3 hours ago
- #innate immunity
- #xenogeneic chimerism
- #organ transplantation
- Organ shortage in transplantation motivates interspecies blastocyst complementation for generating human organs in livestock, but xenogeneic donor cell engraftment faces challenges.
- Xenophagocytosis is identified as an innate immune barrier where host macrophages selectively eliminate viable xenogeneic donor cells, mediated by elevated phosphatidylserine on donor cells recognized via phagocytic receptor Axl.
- Three strategies block xenophagocytosis: genetic ablation of host macrophages or Axl receptor, or donor cell overexpression of CD47 or ATP11C to regulate phosphatidylserine.
- Xenophagocytosis blockade enhances rat and human donor chimerism in mouse embryos and improves interspecies pancreas complementation efficiency.
- This reveals an innate immune mechanism safeguarding species integrity in early embryogenesis and offers insights to boost xenogeneic chimerism for human organ generation.