Circulating Exosomes with Distinct Properties during Chronic Lung Allograft Rejection

Area of Science:

• Immunology
• Transplantation Biology
• Exosome Biology

Background:

• Circulating exosomes carrying donor HLA and lung self-antigens (SAg) are implicated in lung transplant rejection.
• Bronchiolitis obliterans syndrome (BOS) is a major cause of chronic lung allograft dysfunction.

Purpose of the Study:

• To characterize exosomes from lung transplant recipients with BOS versus stable recipients.
• To investigate the immunogenic properties of these exosomes in a murine model.

Main Methods:

• Exosomes were isolated from serum of BOS and stable lung transplant recipients.
• Exosome cargo (SAg, HLA, costimulatory molecules, transcription factors) was analyzed.
• Mice were immunized with exosomes, and antibody and cytokine responses (IL-17, IFN-γ, IL-10) to SAg and HLA were measured.

Main Results:

• Exosomes from BOS recipients contained lung-associated SAg (Kα1T, Col-V), MHC class II, costimulatory molecules, and specific transcription factors, absent in stable recipients.
• Mice immunized with BOS exosomes developed antibodies to SAg and HLA, and increased IL-17 and IFN-γ producing lymphocytes.
• BOS exosome immunization led to reduced IL-10 producing cells compared to stable exosome immunization.

Conclusions:

• Exosomes from BOS patients possess unique immune-stimulating properties.
• These exosomes contribute to alloantigen- and SAg-specific immunity, driving chronic rejection after lung transplantation.