Binding Mechanisms For Donor Dc-derived Exosomes To Cross-dress Of Recipient Dc
1Department of Biochemistry, Southern University of Science and Technology, Shenzhen, China, 2Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Meeting: 2022 American Transplant Congress
Abstract number: 9027
Keywords: Allorecognition, Antigen presentation, Graft survival
Topic: Basic Science » Basic Science » 03 - Antigen Presentation / Allorecognition / Dendritic Cells
Session Information
Session Name: Late Breaking: Basic / Translational
Session Type: Rapid Fire Oral Abstract
Date: Monday, June 6, 2022
Session Time: 3:30pm-5:00pm
Presentation Time: 4:20pm-4:30pm
Location: Hynes Room 313
*Purpose: Our previous evidence suggests donor dendritic cell (DC)-derived exosomes cross-dress recipient DC after heart transplantation in mice. This process plays a critical role in alloantigen presentation and acute rejection initiation. However, the mechanisms by which donor-DC derived exosomes bind recipient DC are yet to be known.
*Methods: To generate donor DC-derived exosomes, C57BL/6 bone marrow-derived DCs (BMDC) are cultured with exosome-free medium and matured by with IFN-γ, IL-1β, TNF-α, CpG, and Poly(I:C) on day 6. Supernatant is collected 48 h later for exosome extraction with an enrichment kit. 4 groups of samples are studied with proteomic and protein-protein interaction (PPI) analysis, which include 1, exosomes from donor immature BMDC (donor immature exosomes); 2, EVs from mature BMDCs (donor mature exosomes); 3, C57BL/6 immature BMDCs (recipient imDC); and 4, B6 mature BMDCs (recipient mDC, matured with the method above).
*Results: Proteomic study of donor DC-derived exosomes reveals over 2700 proteins in the cargoes with quantitativedifference between mature and immature exosomes (89 proteins up-regulated and 34 proteins down-regulated). Similar difference occurs between recipient imDC and mDC with 114 proteins up-regulated and 112 proteins down-regulated. Differences between DC groups and those from exosome groups do not overlap. PPI analysis indicates a large number of potential PPI between EV surface proteins and recipient cell membranes. There are around 720 PPI pairs when comparing either mature exosomes and mDC or mature exosomes and imDC. After excluding relatively low combined core score pairs and embracing co-interaction pairs (mature donor exosome surface proteins interacting with both recipient mDC and imDC), we gain 218 pairs of PPI.
*Conclusions: Our findings illustrate a potential PPI network between donor DC-derived exosomes and recipient DC, which helps explain how donor exosomes bind recipient DC for cross-dressing. Our study also lays the foundation for further investigating potential therapeutic targets to prevent allorecognition and acute rejection.
To cite this abstract in AMA style:
ZHANG L, LI X, LIU J, WEI H, LI C, HUANG A, ZHENG C, LIU Q. Binding Mechanisms For Donor Dc-derived Exosomes To Cross-dress Of Recipient Dc [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/binding-mechanisms-for-donor-dc-derived-exosomes-to-cross-dress-of-recipient-dc/. Accessed November 21, 2024.« Back to 2022 American Transplant Congress