ATC Abstracts

American Transplant Congress abstracts

  • Home
  • Meetings Archive
    • 2022 American Transplant Congress
    • 2021 American Transplant Congress
    • 2020 American Transplant Congress
    • 2019 American Transplant Congress
    • 2018 American Transplant Congress
    • 2017 American Transplant Congress
    • 2016 American Transplant Congress
    • 2015 American Transplant Congress
    • 2013 American Transplant Congress
  • Keyword Index
  • Resources
    • 2021 Resources
    • 2016 Resources
      • 2016 Welcome Letter
      • ATC 2016 Program Planning Committees
      • ASTS Council 2015-2016
      • AST Board of Directors 2015-2016
    • 2015 Resources
      • 2015 Welcome Letter
      • ATC 2015 Program Planning Committees
      • ASTS Council 2014-2015
      • AST Board of Directors 2014-2015
      • 2015 Conference Schedule
  • Search

Accelerated Bronchiolitis Obliterans after Lung Transplant Promoted by the ATG16L1 rs2241880 Mutation is Coupled to Mitochondrial Damage and Metabolic Alterations in Monocyte-Derived Alveolar Macrophages

M. Cano1, D. Zhou2, D. Kreisel3, C. Chen4, K. Pugh2, D. Byers1, R. Hachem1, A. E. Gelman3

1Pulmonary and Critical Care, Washington University, Saint Louis, MO, 2Surgery, Washington University, Saint Louis, MO, 3Surgery and Pathology and Immunology, Washington University, Saint Louis, MO, 4Pulmonary and Critical Care, Southwestern Medical Center, Dallas, TX

Meeting: 2020 American Transplant Congress

Abstract number: 418

Keywords: Antigen presentation, Lung transplantation, Obilterative bronchiolitis, Reactive oxygen species

Session Information

Session Name: Antigen Presentation / Allorecognition / Dendritic Cells

Session Type: Oral Abstract Session

Date: Saturday, May 30, 2020

Session Time: 3:15pm-4:45pm

 Presentation Time: 3:15pm-3:27pm

Location: Virtual

*Purpose: Bronchiolitis obliterans (BOS) remains a major cause of death for lung transplant recipients, and the mechanisms that drive BOS remain poorly understood and require further investigation. It is known that genetically encoded deficiencies in mitophagy, a specialized form of autophagy which targets the removal of damaged mitochondria, promote Parkinson’s disease but it is unclear if they play a role in other chronic diseases such as BOS. Recent work has shown that the rs2241880 mutation in ATG16L1, an autophagy related protein, leads to protein instability resulting in deficiency of ATG16L1 in monocyte-derived macrophages. We previously observed that human lung recipient carriers of rs2241880 had accelerated BOS. Therefore, we analyzed the effects of ATG16L1 deficiency in monocyte-derived alveolar macrophages (Mo-AM) in a mouse orthotopic lung transplant model of BOS.

*Methods: CD11cCreATG16L1flox/flox (ATG16L1Δ/Δ) and control CD11cCre recipients received major MHC-mismatched FVB lungs, with immunosuppression to induce acceptance. Following induced epithelial injury, allografts were assessed for obliterative airway lesions (OB) for up to 28 days. Intragraft Mo-AM were analyzed for bulk RNA sequencing and by FACS for mitochondrial mass and ROS production. Mitophagic flux was visualized by confocal microscopy using Mt-kiema mitophagy reporter mice. Mo-AM were characterized metabolically using a Seahorse XF analyzer.

*Results: ATG16L1Δ/Δ recipients showed severe and accelerated OB compared to controls. RNAseq analysis of ATG16L1Δ/Δ Mo-AM demonstrated a loss of transcripts that encode subunits of mitochondria electron complex I, II and V. Confocal and FACS analysis revealed higher MHCII+, attenuated mitophagic flux, high mitochondrial mass and elevated ROS production in ATG16L1Δ/Δ Mo-AM. In line with these observations were decreased maximal mitochondrial respiratory capacity, lower mitochondrial ATP production and increased utilization of glycolysis, consistent with the metabolic adaptation of an M1 inflammatory phenotype.

*Conclusions: These data reveal a new role for ATG16L1 as a regulator of mitochondrial quality control with implications for lung recipients that carry the ATG16L1 rs2241880 mutation.

  • Tweet
  • Email
  • Print

To cite this abstract in AMA style:

Cano M, Zhou D, Kreisel D, Chen C, Pugh K, Byers D, Hachem R, Gelman AE. Accelerated Bronchiolitis Obliterans after Lung Transplant Promoted by the ATG16L1 rs2241880 Mutation is Coupled to Mitochondrial Damage and Metabolic Alterations in Monocyte-Derived Alveolar Macrophages [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/accelerated-bronchiolitis-obliterans-after-lung-transplant-promoted-by-the-atg16l1-rs2241880-mutation-is-coupled-to-mitochondrial-damage-and-metabolic-alterations-in-monocyte-derived-alveolar-macropha/. Accessed May 9, 2025.

« Back to 2020 American Transplant Congress

Visit Our Partner Sites

American Transplant Congress (ATC)

Visit the official site for the American Transplant Congress »

American Journal of Transplantation

The official publication for the American Society of Transplantation (AST) and the American Society of Transplant Surgeons (ASTS) »

American Society of Transplantation (AST)

An organization of more than 3000 professionals dedicated to advancing the field of transplantation. »

American Society of Transplant Surgeons (ASTS)

The society represents approximately 1,800 professionals dedicated to excellence in transplantation surgery. »

Copyright © 2013-2025 by American Society of Transplantation and the American Society of Transplant Surgeons. All rights reserved.

Privacy Policy | Terms of Use | Cookie Preferences