Specific Requirement of the p84/p110γ Complex of PI3Kγ for Antibody-Activated, Inducible Cross-Presentation in Murine Type 2 DCs.

Autor: Koumantou D; Centre de Recherche sur l'Inflammation, INSERM UMR1149, CNRS EMR8252, Faculté de Médecine site Bichat, Université Paris Cité, Paris, 75018, France.; Laboratoire d'Excellence Inflamex, Université Paris Cité, Paris, 75018, France., Adiko AC; Centre de Recherche sur l'Inflammation, INSERM UMR1149, CNRS EMR8252, Faculté de Médecine site Bichat, Université Paris Cité, Paris, 75018, France.; Laboratoire d'Excellence Inflamex, Université Paris Cité, Paris, 75018, France., Bourdely P; Centre de Recherche sur l'Inflammation, INSERM UMR1149, CNRS EMR8252, Faculté de Médecine site Bichat, Université Paris Cité, Paris, 75018, France.; CNRS, INSERM, Institut Cochin, Paris, 75014, France., Nugue M; Centre de Recherche sur l'Inflammation, INSERM UMR1149, CNRS EMR8252, Faculté de Médecine site Bichat, Université Paris Cité, Paris, 75018, France.; Laboratoire d'Excellence Inflamex, Université Paris Cité, Paris, 75018, France., Boedec E; Centre de Recherche sur l'Inflammation, INSERM UMR1149, CNRS EMR8252, Faculté de Médecine site Bichat, Université Paris Cité, Paris, 75018, France.; Laboratoire d'Excellence Inflamex, Université Paris Cité, Paris, 75018, France., El-Benna J; Centre de Recherche sur l'Inflammation, INSERM UMR1149, CNRS EMR8252, Faculté de Médecine site Bichat, Université Paris Cité, Paris, 75018, France.; Laboratoire d'Excellence Inflamex, Université Paris Cité, Paris, 75018, France., Monteiro R; Centre de Recherche sur l'Inflammation, INSERM UMR1149, CNRS EMR8252, Faculté de Médecine site Bichat, Université Paris Cité, Paris, 75018, France.; Laboratoire d'Excellence Inflamex, Université Paris Cité, Paris, 75018, France., Saveanu C; Institut Pasteur, RNA Biology of Fungal Pathogens, Université Paris Cité, Paris, 75015, France., Laffargue M; INSERM UMR 1048, I2MC, Toulouse, 4 31432, France., Wymann MP; Department of Biomedicine, University of Basel, Mattenstrasse 28, Basel, CH-4058, Switzerland., Dalod M; CNRS, INSERM, CIML, Centre d'Immunologie de Marseille-Luminy, Turing Center for Living Systems, Aix-Marseille University, Marseille, 13007, France., Guermonprez P; 'Dendritic cells and adaptive immunity', Immunology department, Pasteur Institute, Paris, 75015, France.; CNRS UMR3738, Département Biologie du Développement et Cellules Souches, Institut Pasteur, Université Paris Cité, 25-28 rue du Docteur Roux, Paris, 75015, France., Saveanu L; Centre de Recherche sur l'Inflammation, INSERM UMR1149, CNRS EMR8252, Faculté de Médecine site Bichat, Université Paris Cité, Paris, 75018, France.; Laboratoire d'Excellence Inflamex, Université Paris Cité, Paris, 75018, France.
Jazyk: angličtina
Zdroj: Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Adv Sci (Weinh)] 2024 Oct 09, pp. e2401179. Date of Electronic Publication: 2024 Oct 09.
DOI: 10.1002/advs.202401179
Abstrakt: Cross-presentation by MHCI is optimally efficient in type 1 dendritic cells (DC) due to their high capacity for antigen processing. However, through specific pathways, other DCs, such as type 2 DCs and inflammatory DCs (iDCs) can also cross-present antigens. FcγR-mediated uptake by type 2 DC and iDC subsets mediates antibody-dependent cross-presentation and activation of CD8 + T cell responses. Here, an important role for the p84 regulatory subunit of PI3Kγ in mediating efficient cross-presentation of exogenous antigens in otherwise inefficient cross-presenting cells, such as type 2 DCs and GM-CSF-derived iDCs is identified. FcγR-mediated cross-presentation is shown in type 2 and iDCs depend on the enzymatic activity of the p84/p110γ complex of PI3Kγ, which controls the activity of the NADPH oxidase NOX2 and ROS production in murine spleen type 2 DCs and GM-CSF-derived iDCs. In contrast, p84/p110γ is largely dispensable for cross-presentation by type 1 DCs. These findings suggest that PI3Kγ-targeted therapies, currently considered for oncological practice, may interfere with the ability of type 2 DCs and iDCs to cross-present antigens contained in immune complexes.
(© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)
Databáze: MEDLINE
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