ABSTRACT
Macroautophagy (often-named autophagy), a catabolic process involving autophagy-related (Atg) genes, prevents accumulation of harmful cytoplasmic components and mobilizes energy reserves in long-lived and self-renewing cells. Autophagy deficiency affects antigen presentation in conventional dendritic cells (DCs) without impacting their survival. However, previous studies did not address epidermal Langerhans cells (LCs). Here, we demonstrate that deletion of either Atg5 or Atg7 in LCs leads to their gradual depletion. ATG5-deficient LCs showed metabolic dysregulation and accumulated neutral lipids. Despite increased mitochondrial respiratory capacity, they were unable to process lipids, eventually leading them to ferroptosis. Finally, metabolically impaired LCs upregulated proinflammatory transcripts and showed decreased expression of neuronal interaction receptors. Altogether, autophagy represents a critical regulator of lipid storage and metabolism in LCs, allowing their maintenance in the epidermis.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
↵#, * Equal contribution
All modifications in the text have been highlighted. The age of mice and information about heatmaps has been added to Figure legends. Quantification of intracellular ferrous iron by the FerroOrange assay in LCs is now included in Figure 6C. Figure 8 has been modified and is now supplied as Figure S6.