The immune “checkpoint” pathway includes the receptor Programmed cell death protein 1 (PD-1) and its ligand Programmed death-ligand 1 (PD-L1). The binding of PD-L1 to PD-1 leads to negative regulation of T cell receptor signaling.
We have found that patients with Acute Respiratory Distress Syndrome (ARDS) who have prolonged mechanical ventilation have lower expression of PD-L1 on alveolar macrophages. Further, a serious side effect of pharmaceutical inhibitors of this pathway termed “checkpoint inhibitors” is immune mediated tissue injury such as an ARDS-like pneumonitis. Thus the role of this pathway in modulating immune responses is critical to our understanding of ARDS.
We are studying how PD-L1 affects macrophage function and the effects on T cell responses in primary bronchoalveolar lavage samples from patients with ARDS.
