The PD-1/PD-L1 pathway maintains an immunosuppressive environment essential for neonatal heart regeneration [scRNA-seq]

The adult heart responds to injury by scarring with consequent loss of contractile function, whereas the neonatal heart possesses the ability to regenerate. We compared the immune response to injury in neonatal and adult mouse hearts and discovered that the PD1/PD-L1 immune checkpoint pathway is highly activated in regenerative hearts but is silenced in later life. Deletion of the PD1 receptor or inactivation of its PD-L1 ligand prevented regeneration of neonatal hearts after injury. Our findings reveal a previously unrecognized role of the PD1/PD-L1 pathway in the control of heart regeneration through modulating T cell activity and inflammation following injury and provide new inroads into the control of adult tissue regeneration. We analyzed the transcriptome of CD45+ immune cells from PD1 homozygous and heterozygous deletion mice at 7 days after either myocardial infarction or sham surgery performed at P2.