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

Published in: Adv Sci (Weinh) 2024 Nov; 11(44): e2401179

Authors: Despoina Koumantou, Aimé Cézaire Adiko, Pierre Bourdely, Mathilde Nugue, Erwan Boedec, Jamel El-Benna, Renato Monteiro, Cosmin Saveanu, Muriel Laffargue, Matthias P Wymann, Marc Dalod, Pierre Guermonprez, Loredana Saveanu

Summary

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.

Link to Pubmed [PMID] – 39382167

Link to HAL – amu-04932271

Link to DOI – 10.1002/advs.202401179