Project description:This is an RNA-seq study of human lung transplant recipients. Bronchoalveolar lavage cells were collected on the first day after lung transplant. We performed bulk RNA-sequencing on 19 lung transplant recipients with severe primary graft dysfunction (PGD) and 19 lung transplant recipients without primary graft dysfunction. As this data is human identifiable, raw data are not included in this record.
Project description:Chronic lung allograft dysfunction (CLAD) is the leading cause of death in lung transplant recipients. CLAD is characterized clinically by a persistent decline in pulmonary function and histologically by the development of airway centered fibrosis known as bronchiolitis obliterans. We performed single-cell sequencing and spatial transcriptomic analysis of explanted tissues from human lung recipients with CLAD and donor control lungs.
Project description:Tissue resident memory T cells (TRM) maintain immunity in diverse sites as determined in mouse models, while their establishment and role in human tissues has been difficult to assess. Here, we investigated human lung TRM generation, maintenance and function in airway samples obtained longitudinally from HLA-disparate lung transplant recipients, where donor and recipient T cells could be localized and tracked over time. Donor T cells persist specifically in the lungs (and not blood) of transplant recipients and express high levels of TRM signature markers including CD69, CD103, and CD49a, while lung-infiltrating recipient T cells gradually acquire TRM phenotypes over months in vivo. Single cell transcriptome profiling of airway T cells reveals that donor T cells comprise two TRM-like subsets with varying levels of expression of TRM-associated genes while recipient T cells comprised non-TRM and similar TRM-like subpopulations, suggesting de novo TRM generation. Transplant recipients exhibiting higher frequencies of persisting donor TRM experienced fewer adverse clinical events such as primary graft dysfunction and acute cellular rejection compared to recipients with low donor TRM persistence, suggesting that monitoring TRM dynamics could be clinically informative. Together, our results provide novel spatial and temporal insights into how human TRM develop, function, persist, and impact tissue integrity within the complexities of lung transplantation.
Project description:Chronic Lung Allograft Dysfunction (CLAD) is the main limitation to long-term survival after lung transplantation. Although CLAD is usually not responsive to treatment, earlier identification may improve treatment prospects. In a nested case control study, 1-year post transplant surveillance bronchoalveolar lavage (BAL) fluid samples were obtained from incipient CLAD (n=9) and CLAD free (n=8) lung transplant recipients. Incipient CLAD cases were diagnosed with CLAD within 2 years, while controls were free from CLAD for at least 4 years following bronchoscopy. Transcription profiles in the BAL cell pellets were assayed with the HG-U133 Plus 2.0 microarray (Affymetrix). Differential gene expression analysis was performed to identify a candidate list of differentially expressed probe sets.
Project description:TransplantLines is designed as a single-center, prospective cohort study and biobank including all different types of solid organ transplant recipients as well as living organ donors. In the TransplantLines gut microbiome study the gut microbiome of solid organ transplant recipients is characterized and linked to clinical phenotypes. This batch contains the cross-sectional data from liver transplant recipients and longitudinal data from renal and liver transplant recipients.