Peroxisome deficiency underlies failures in hepatic immune cell development and antigen presentation in a severe Zellweger disease model
Brendon D. Parsons,
Daniel Medina-Luna,
Michal Scur,
Marinella Pinelli,
Gayani S. Gamage,
Rebecca A. Chilvers,
Yannick Hamon,
Ibrahim H.I. Ahmed,
Stéphane Savary,
Andrew P. Makrigiannis,
Nancy E. Braverman,
Juan F. Rodriguez-Alcazar,
Eicke Latz,
Tobias K. Karakach,
Francesca Di Cara
Affiliations
Brendon D. Parsons
University of Alberta, Department of Laboratory Medicine and Pathology, Edmonton, AB T6G 1C9, Canada
Daniel Medina-Luna
Dalhousie University, Department of Microbiology and Immunology, Halifax, NS B3K 6R8, Canada
Michal Scur
Dalhousie University, Department of Microbiology and Immunology, Halifax, NS B3K 6R8, Canada
Marinella Pinelli
Dalhousie University, Department of Microbiology and Immunology, Halifax, NS B3K 6R8, Canada
Gayani S. Gamage
Dalhousie University, Department of Microbiology and Immunology, Halifax, NS B3K 6R8, Canada
Rebecca A. Chilvers
Dalhousie University, Department of Microbiology and Immunology, Halifax, NS B3K 6R8, Canada
Yannick Hamon
Aix Marseille University, CNRS, INSERM au Centre d'Immunologie de Marseille Luminy, 13288 Marseille, France
Ibrahim H.I. Ahmed
Dalhousie University, Department of Pharmacology, Halifax, NS B3H 4R2, Canada; Beatrice Hunter Cancer Research Institute, Halifax, NS, Canada
Stéphane Savary
University of Bourgogne, Laboratoire Bio-PeroxIL EA7270, Dijon, France
Andrew P. Makrigiannis
Dalhousie University, Department of Microbiology and Immunology, Halifax, NS B3K 6R8, Canada; Beatrice Hunter Cancer Research Institute, Halifax, NS, Canada
Nancy E. Braverman
Research Institute of the McGill University Children’s Hospital, Montreal, QC H4A 3J1, Canada
Juan F. Rodriguez-Alcazar
University of Bonn, Institute of Innate Immunity, Medical Faculty, 53127 Bonn, Germany
Eicke Latz
University of Bonn, Institute of Innate Immunity, Medical Faculty, 53127 Bonn, Germany
Tobias K. Karakach
Dalhousie University, Department of Pharmacology, Halifax, NS B3H 4R2, Canada; Beatrice Hunter Cancer Research Institute, Halifax, NS, Canada
Francesca Di Cara
University of Alberta, Department of Laboratory Medicine and Pathology, Edmonton, AB T6G 1C9, Canada; Beatrice Hunter Cancer Research Institute, Halifax, NS, Canada; Corresponding author
Summary: Peroxisome biogenesis disorders (PBDs) represent a group of metabolic conditions that cause severe developmental defects. Peroxisomes are essential metabolic organelles, present in virtually every eukaryotic cell and mediating key processes in immunometabolism. To date, the full spectrum of PBDs remains to be identified, and the impact PBDs have on immune function is unexplored. This study presents a characterization of the hepatic immune compartment of a neonatal PBD mouse model at single-cell resolution to establish the importance and function of peroxisomes in developmental hematopoiesis. We report that hematopoietic defects are a feature in a severe PBD murine model. Finally, we identify a role for peroxisomes in the regulation of the major histocompatibility class II expression and antigen presentation to CD4+ T cells in dendritic cells. This study adds to our understanding of the mechanisms of PBDs and expands our knowledge of the role of peroxisomes in immunometabolism.
