Abstract

Lung transplantation (LTx) is often the last remaining therapeutic option for patients with end-stage lung diseases, such as idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, or pulmonary hypertension. Despite numerous advances in the field of transplant surgery and follow-up care, the mean graft survival after LTx remains significantly limited at about 7 years. Clinicians and recipients are still challenged by various complications such as cellular or humoral rejection. Nevertheless, we could identify a group of patients that live for years without any complication after LTx, termed ?super survivors?. On the histological level, this group is characterized by a high number of alveolar macrophages despite the lack of clinical signs of infection or pulmonary remodelling. To investigate the role of the innate immune system with macrophages as major players in graft tolerance, we analyzed lung tissue from transbronchial biopsies. Therefore a whole transcriptome analysis of alveolar macrophages in n=16 super survivors as well as n=12 healthy controls was performed using the novel Nanostring GeoMx spatial transcriptomics technology. We identified a specific gene expression pattern in alveolar macrophages from LTx super survivors, distinct from the classical M1-M2 scheme. Here, we found macrophages exhibiting characteristics of anti-arteriosclerotic and anti-inflammatory macrophages in the context of long-term survival after LTx. We speculate that these macrophages have a protective effect on the allograft.