NKG2D receptor activation drives primary graft dysfunction severity and poor lung transplantation outcomes

• DOI: 10.1172/jci.insight.164603
• Publication Date: 2022-11-08T17:06:00Z
• Authors: Daniel R. Calabrese; Tasha Tsao; Mélia Magnen; Colin Valet; Ying Gao; Beñat Mallavia; Jennifer J. Tian; Emily A. Aminian; Kristin M. Wang; Avishai Shemesh; Elman B. Punzalan; Aartik Sarma; Carolyn S. Calfee; Stephanie A. Chri...; Charles R. Langelier; Steven R. Hays; Jeffrey A. Golden; Lorriana E. Leard; Mary Ellen Kleinhenz; Nicholas A. Kolaitis; Rupal Shah; Aida Venado; Lewis L. Lanier; John R. Greenland; David M. Sayah; Abbas Ardehali; Jasleen Kukreja; S. Samuel Weigt; John A. Belperio; Jonathan P. Singer; Mark R. Looney
• Keywords: NKG2D

Clinical outcomes after lung transplantation, a life-saving therapy for patients with end-stage diseases, are limited by primary graft dysfunction (PGD). PGD is an early form of acute injury no specific pharmacologic therapies. Here, we present large multicenter study plasma and bronchoalveolar lavage (BAL) samples collected on the first posttransplant day, critical time investigations immune pathways related to PGD. We demonstrated that ligands NKG2D receptors were increased in BAL from participants who developed severe associated extubation, prolonged intensive care unit length stay, poor peak function. Neutrophil extracellular traps (NETs) correlated TNF-α IFN-γ cytokines. Mechanistically, found airway epithelial cell following hypoxic challenge. NK killing cells was abrogated receptor blockade, provoked neutrophils release NETs culture. These data support aberrant cell/neutrophil axis human pathogenesis. Early measurement stress blockade hold promise risk stratification management