Deficiency in peroxisomes underlies failures in neonatal hepatic immune cell hematopoiesis and antigen presentation in a severe Zellweger disease model
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. Overall design: Liver immune cells from pex2 homozygous null mutant, pex2 heterozygous, and wildtype neonatal mice were isolated by Fluorescence-activeated cell sorting (FACs) according to fluorescence-conjugted anti-CD45 antibody labelling and viability staining and analyzed using scRNAseq.