Epidermal maintenance of Langerhans cells relies on autophagy-regulated lipid metabolism
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.
Authors
- Wacym Boufenghour (ORCID: https://orcid.org/0000-0002-2018-3102)
- Hélène Puccio (ORCID: https://orcid.org/0000-0003-4711-2248)
- Benjamin Voisin (ORCID: https://orcid.org/0000-0003-1314-2908)
- Emmanuel L. Gautier (ORCID: https://orcid.org/0000-0003-2976-7566)
- Raquel Sal-Carro (ORCID: https://orcid.org/0000-0002-4324-5409)
- Björn E. Clausen (ORCID: https://orcid.org/0000-0002-2484-7842)
- Seiamak Bahram (ORCID: https://orcid.org/0000-0002-6928-9952)
- Rebecca Fima (ORCID: https://orcid.org/0000-0002-1150-1260)
- Jean‐Daniel Fauny (ORCID: https://orcid.org/0000-0002-1651-8555)
- Thierry Huby (ORCID: https://orcid.org/0000-0001-6634-551X)
- Louise Filippi de la Palavesa (ORCID: https://orcid.org/0000-0002-4470-5884)
- Olivier Griso
- Vincent Flacher (ORCID: https://orcid.org/0000-0002-8648-2615)
- Florent Arbogast
- Delphine Bouis (ORCID: https://orcid.org/0000-0002-4917-3135)
- Frédéric Gros (ORCID: https://orcid.org/0000-0002-6252-4323)
- Raphaël Carapito (ORCID: https://orcid.org/0000-0002-7036-442X)
- Anne Molitor (ORCID: https://orcid.org/0000-0003-1646-2325)
- Nikolaus Romani (ORCID: https://orcid.org/0000-0003-1614-9128)
- Quentin Frenger (ORCID: https://orcid.org/0000-0002-2057-3813)
- Christopher G. Mueller (ORCID: https://orcid.org/0000-0002-4119-2729)
Institutions
- Innsbruck Medical University (AT)
- Inserm (FR)
- Universität Innsbruck (AT)
- Johannes Gutenberg University Mainz (DE)
- Sorbonne Université (FR)
- Institut de génétique et de biologie moléculaire et cellulaire (FR)
- University Medical Center of the Johannes Gutenberg University Mainz (DE)
- Hôpitaux Universitaires de Strasbourg (FR)
- Institute for Molecular Medicine (US)
- Institut de Biologie Moléculaire et Cellulaire (FR)
- Hôpital Civil, Strasbourg (FR)
- Université de Strasbourg (FR)
Publication Details
- Journal
- The Journal of Cell Biology
- Published
- 2024-10-24
- DOI
- https://doi.org/10.1083/jcb.202403178
- Citations
- 1
- Primary Topic
- Autophagy in Disease and Therapy
- Type
- article
- Field-Weighted Citation Impact
- 0.39
Funders
- International Business Machines Corporation
- Fondation Arthritis
- Equipex
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Université de Strasbourg
- Centre National de la Recherche Scientifique
- H2020 Marie Skłodowska-Curie Actions