bims-nocaut Biomed News
on Non-canonical autophagy
Issue of 2025–06–01
two papers selected by
Quentin Frenger, University of Strasbourg
  1. ATG5 controls CD80 expression in B cells and shapes cognate CD4+ T cell responses.
  2. Extracellular Vesicles in the Crosstalk of Autophagy and Apoptosis: A Role for Lipid Rafts.
  1. Autophagy. 2025 May 27. 1-9
    ATG5 controls CD80 expression in B cells and shapes cognate CD4+ T cell responses.
    Ingredy Passos, Thomas Zobel, Christian Münz, Anneli Peters, Jan D Lünemann.
      The macroautophagy/autophagy machinery has been implicated in supporting MHC class II but compromising MHC class I restricted antigen presentation by dendritic cells (DCs). Here, we report that loss of the essential autophagy protein ATG5 in B cells reduces internalization and stabilizes co-stimulatory CD80 surface expression. In an adjuvant-free experimental autoimmune encephalomyelitis (EAE) mouse model, co-transfer of MOG-specific induced germinal center B (iGB) cells deficient in ATG5 with MOG-specific CD4+ T cells, accelerated disease development. CD80 blockade abrogated enhanced cognate CD4+ T-cell responses induced by iGB cells lacking ATG5. These data broaden the concept of ATG5-mediated antigen presentation and indicate that ATG5 might not only enhance, as described previously with MHC class II-restricted presentation in DCs, but also limit the activation of CD4+ T cells through attenuating CD80 expression on B cells.Abbreviations: APC: antigen-presenting cell; CNS: central nervous system; DC: dendritic cell; EAE: experimental autoimmune encephalomyelitis; iGB: induced germinal center B cell; MOG: myelin oligodendrocyte glycoprotein; MS: multiple sclerosis.
    Keywords:  Antigen presentation; B- and T-cell interaction; autoimmunity; autophagy proteins; central nervous system; multiple sclerosis
    DOI:  https://doi.org/10.1080/15548627.2025.2507614
  2. Cells. 2025 05 20. pii: 749. [Epub ahead of print]14(10):
    Extracellular Vesicles in the Crosstalk of Autophagy and Apoptosis: A Role for Lipid Rafts.
    Agostina Longo, Valeria Manganelli, Roberta Misasi, Gloria Riitano, Tuba Rana Caglar, Elena Fasciolo, Serena Recalchi, Maurizio Sorice, Tina Garofalo.
      Autophagy and apoptosis are two essential mechanisms regulating cell fate. Although distinct, their signaling pathways are closely interconnected through various crosstalk mechanisms. Lipid rafts are described to act as both physical and functional platforms during the early stages of autophagic and apoptotic processes. Only recently has a role for lipid raft-associated molecules in regulating EV biogenesis and release begun to emerge. In particular, lipids of EV membranes are essential components in conferring stability to these vesicles in different extracellular environments and/or to facilitate binding or uptake into recipient cells. In this review we highlight these aspects, focusing on the role of lipid molecules during apoptosis and secretory autophagy pathways. We describe the molecular machinery that connects autophagy and apoptosis with vesicular trafficking and lipid metabolism during the release of EVs, and how their alterations contribute to the development of various diseases, including autoimmune disorders and cancer. Overall, these findings emphasize the complexity of autophagy/apoptosis crosstalk and its key role in cellular dynamics, supporting the role of lipid rafts as new therapeutic targets.
    Keywords:  apoptosis; autophagy; exosomes; extracellular vesicles; lipid rafts
    DOI:  https://doi.org/10.3390/cells14100749
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