Lung Innate Lymphoid Cell Composition Is Altered in Primary Graft Dysfunction

Rationale: Primary graft dysfunction (PGD) is the leading cause of early morbidity and mortality after lung transplantation, but the immunologic mechanisms are poorly understood. Innate lymphoid cells (ILC) are a heterogeneous family of immune cells regulating pathologic inflammation and beneficial tissue repair. However, whether changes in donor-derived lung ILC populations are associated with PGD development has never been examined.Objectives: To determine whether PGD in chronic obstructive pulmonary disease or interstitial lung disease transplant recipients is associated with alterations in ILC subset composition within the allograft.Methods: We performed a single-center cohort study of lung transplantation patients with surgical biopsies of donor tissue taken before, and immediately after, allograft reperfusion. Donor immune cells from 18 patients were characterized phenotypically by flow cytometry for single-cell resolution of distinct ILC subsets. Changes in the percentage of ILC subsets with reperfusion or PGD (grade 3 within 72 h) were assessed.Measurements and Main Results: Allograft reperfusion resulted in significantly decreased frequencies of natural killer cells and a trend toward reduced ILC populations, regardless of diagnosis (interstitial lung disease or chronic obstructive pulmonary disease). Seven patients developed PGD (38.9%), and PGD development was associated with selective reduction of the ILC2 subset after reperfusion. Conversely, patients without PGD exhibited significantly higher ILC1 frequencies before reperfusion, accompanied by elevated ILC2 frequencies after allograft reperfusion.Conclusions: The composition of donor ILC subsets is altered after allograft reperfusion and is associated with PGD development, suggesting that ILCs may be involved in regulating lung injury in lung transplant recipients.