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. 2015 Dec 15;192(12):1490-503.
doi: 10.1164/rccm.201503-0558OC.

Altered Exosomal RNA Profiles in Bronchoalveolar Lavage from Lung Transplants with Acute Rejection

Aric L Gregson  1 , Aki Hoji  2 , Patil Injean  3 , Steven T Poynter  3 , Claudia Briones  3 , Vyacheslav Palchevskiy  3 , S Sam Weigt  3 , Michael Y Shino  3 , Ariss Derhovanessian  3 , David Sayah  3 , Rajan Saggar  3 , David Ross  3 , Abbas Ardehali  4 , Joseph P Lynch 3rd  3 , John A Belperio  3
Affiliations

Altered Exosomal RNA Profiles in Bronchoalveolar Lavage from Lung Transplants with Acute Rejection

Aric L Gregson et al. Am J Respir Crit Care Med. .

Abstract

Rationale: The mechanism by which acute allograft rejection leads to chronic rejection remains poorly understood despite its common occurrence. Exosomes, membrane vesicles released from cells within the lung allograft, contain a diverse array of biomolecules that closely reflect the biologic state of the cell and tissue from which they are released. Exosome transcriptomes may provide a better understanding of the rejection process. Furthermore, biomarkers originating from this transcriptome could provide timely and sensitive detection of acute cellular rejection (AR), reducing the incidence of severe AR and chronic lung allograft dysfunction and improving outcomes.

Objectives: To provide an in-depth analysis of the bronchoalveolar lavage fluid exosomal shuttle RNA population after lung transplantation and evaluate for differential expression between acute AR and quiescence.

Methods: Serial bronchoalveolar lavage specimens were ultracentrifuged to obtain the exosomal pellet for RNA extraction, on which RNA-Seq was performed.

Measurements and main results: AR demonstrates an intense inflammatory environment, skewed toward both innate and adaptive immune responses. Novel, potential upstream regulators identified offer potential therapeutic targets.

Conclusions: Our findings validate bronchoalveolar lavage fluid exosomal shuttle RNA as a source for understanding the pathophysiology of AR and for biomarker discovery in lung transplantation.

Keywords: RNA; exosome; rejection; lung; transplantation.

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Figures

Figure 1.
Figure 1.
Quiescent-samples Reactome results for the bronchoalveolar lavage fluid exosomes analyzed by Limma group-means parameterization. The number of altered genes in a particular pathway is given on the x-axis.
Figure 2.
Figure 2.
Reactome results for exosomes from acute rejection samples analyzed by Limma group-means parameterization. The number of altered genes in a particular pathway is given on the x-axis.
Figure 3.
Figure 3.
Example pathway from Generally Applicable Gene-set Enrichment Kyoto Encyclopedia of Genes and Genomes analysis of exosomal shuttle RNA. Representative example of natural killer cell–mediated cytotoxicity comparing rejection (left) and quiescent (right) conditions.
Figure 4.
Figure 4.
Ingenuity Pathway Analysis canonical pathways enriched by genes differentially expressed in acute cellular rejection samples in exosomal shuttle RNA.
See this image and copyright information in PMC

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