1. Epidermal maintenance of Langerhans cells relies on autophagy-regulated lipid metabolism.
- Author
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Arbogast F, Sal-Carro R, Boufenghour W, Frenger Q, Bouis D, Filippi De La Palavesa L, Fauny JD, Griso O, Puccio H, Fima R, Huby T, Gautier EL, Molitor A, Carapito R, Bahram S, Romani N, Clausen BE, Voisin B, Mueller CG, Gros F, and Flacher V
- Subjects
- Animals, Mice, Mice, Inbred C57BL, Mice, Knockout, Mitochondria metabolism, Langerhans Cells metabolism, Autophagy, Lipid Metabolism, Epidermis metabolism, Autophagy-Related Protein 7 genetics, Autophagy-Related Protein 7 metabolism, Autophagy-Related Protein 5 metabolism, Autophagy-Related Protein 5 genetics
- Abstract
Macroautophagy (often-named autophagy), a catabolic process involving autophagy-related (Atg) genes, prevents the 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., (© 2024 Arbogast et al.)
- Published
- 2025
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