Irradiation‐Induced CD62L Shedding in Human Plasmacytoid Dendritic Cells Depends on ADAM17 and p38 MAPK
6 affiliations
- 1PDC*Line Pharma SAS Grenoble France
- 2Université Grenoble Alpes, CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMC Grenoble France
- 3Université Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Institute for Advanced Biosciences (IAB), Team Translational Immunology and Immunotherapy in Chronic Disease Grenoble France
- 4Recherche et Développement, Etablissement Français du Sang Auvergne‐Rhône‐Alpes Grenoble France
- 5TransCure bioServices Archamps France
- 6Université Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Institute for Advanced Biosciences (IAB), Optimal Grenoble France
Abstract
Plasmacytoid dendritic cells (PDCs) represent a crucial bridge between innate and adaptive immunity as they can recognise viruses and viral‐infected cells, secrete type I interferon and prime naive T‐cell responses. Like naive T cells, PDCs express CD62L, an essential molecule involved in the trans‐endothelial migration process, and are supposed to travel directly from blood to lymph nodes to prime naive T cells. We developed a therapeutic PDC line model (PDC*line) derived from a patient with blastic PDC neoplasm, and showing high antigen‐presentation capacities. PDC*line‐based vaccine was tested in clinical trials in melanoma and lung cancer. Efficient specific T lymphocyte priming was observed suggesting the efficient migration of injected PDC*line‐based vaccine to lymph nodes. Here, we investigated the mechanisms involved in this migration and its regulation. In humanised mice, our results demonstrated the efficient migration of the PDC‐based vaccine from blood to lymph nodes and its capacity to prime naive T cells. The expression of CD62L was evaluated following irradiation, which was mandatory in the vaccine manufacturing step and possibly important for its efficacy. CD62L was rapidly shed after irradiation of PDC*line cells and primary PDCs but not of NK‐T cells, demonstrating the cell specificity of the mechanism. Our results show that p38 MAP kinase, known to be activated in response to irradiation and ADAM17 metalloprotease are involved in the rapid CD62L shedding. This new pathway could participate to the regulation PDC transmigration through High Endothelial Venules and homing to secondary lymphoid organs in cellular stress conditions.
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BibTeX
@article{leplus2026irradiationinduced,
title = {{Irradiation‐Induced CD62L Shedding in Human Plasmacytoid Dendritic Cells Depends on ADAM17 and p38 MAPK}},
author = {Estelle Leplus and Jamila Kacher and Dalil Hannani and Guillaume Vayssiere and Jean‐Paul Molens and Karine Laulanier and Dan Georgess and Véronique Josserand and Philippe Saas and Séverine Planel and Laurence Chaperot and Joel Plumas},
journal = {Immunology},
year = {2026},
month = sep,
doi = {10.1111/imm.70194},
url = {https://doi.org/10.1111/imm.70194},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Irradiation‐Induced CD62L Shedding in Human Plasmacytoid Dendritic Cells Depends on ADAM17 and p38 MAPK
AU - Estelle Leplus
AU - Jamila Kacher
AU - Dalil Hannani
AU - Guillaume Vayssiere
AU - Jean‐Paul Molens
AU - Karine Laulanier
AU - Dan Georgess
AU - Véronique Josserand
AU - Philippe Saas
AU - Séverine Planel
AU - Laurence Chaperot
AU - Joel Plumas
PY - 2026
DA - 2026/09/02
JO - Immunology
DO - 10.1111/imm.70194
UR - https://doi.org/10.1111/imm.70194
AB - Plasmacytoid dendritic cells (PDCs) represent a crucial bridge between innate and adaptive immunity as they can recognise viruses and viral‐infected cells, secrete type I interferon and prime naive T‐cell responses. Like naive T cells, PDCs express CD62L, an essential molecule involved in the trans‐endothelial migration process, and are supposed to travel directly from blood to lymph nodes to prime naive T cells. We developed a therapeutic PDC line model (PDC*line) derived from a patient with blastic PDC neoplasm, and showing high antigen‐presentation capacities. PDC*line‐based vaccine was tested in clinical trials in melanoma and lung cancer. Efficient specific T lymphocyte priming was observed suggesting the efficient migration of injected PDC*line‐based vaccine to lymph nodes. Here, we investigated the mechanisms involved in this migration and its regulation. In humanised mice, our results demonstrated the efficient migration of the PDC‐based vaccine from blood to lymph nodes and its capacity to prime naive T cells. The expression of CD62L was evaluated following irradiation, which was mandatory in the vaccine manufacturing step and possibly important for its efficacy. CD62L was rapidly shed after irradiation of PDC*line cells and primary PDCs but not of NK‐T cells, demonstrating the cell specificity of the mechanism. Our results show that p38 MAP kinase, known to be activated in response to irradiation and ADAM17 metalloprotease are involved in the rapid CD62L shedding. This new pathway could participate to the regulation PDC transmigration through High Endothelial Venules and homing to secondary lymphoid organs in cellular stress conditions.
SN - 0019-2805
SN - 1365-2567
ER -