New insights into the immunomodulatory potential of sialic acid on monocyte-derived dendritic cells.

Autor: Silva Z; Associate Laboratory i4HB, NOVA School of Science and Technology, Institute for Health and Bioeconomy, Universidade NOVA de Lisboa, 2829-516, Caparica, Portugal.; Department of Life Sciences, Applied Molecular Biosciences Unit, UCIBIO, NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2829-516, Caparica, Portugal., Rabaça JA; Associate Laboratory i4HB, NOVA School of Science and Technology, Institute for Health and Bioeconomy, Universidade NOVA de Lisboa, 2829-516, Caparica, Portugal.; Department of Life Sciences, Applied Molecular Biosciences Unit, UCIBIO, NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2829-516, Caparica, Portugal., Luz V; Associate Laboratory i4HB, NOVA School of Science and Technology, Institute for Health and Bioeconomy, Universidade NOVA de Lisboa, 2829-516, Caparica, Portugal.; Department of Life Sciences, Applied Molecular Biosciences Unit, UCIBIO, NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2829-516, Caparica, Portugal., Lourenço RA; Associate Laboratory i4HB, NOVA School of Science and Technology, Institute for Health and Bioeconomy, Universidade NOVA de Lisboa, 2829-516, Caparica, Portugal.; Department of Life Sciences, Applied Molecular Biosciences Unit, UCIBIO, NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2829-516, Caparica, Portugal., Salio M; Medical Research Council Translational Immune Discovery Unit, Medical Research Council Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX39DS, UK., Oliveira AC; CIISA‑Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, Avenida da Universidade Técnica, 1300‑477, Lisbon, Portugal.; Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1300‑477, Lisbon, Portugal., Bule P; CIISA‑Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, Avenida da Universidade Técnica, 1300‑477, Lisbon, Portugal.; Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1300‑477, Lisbon, Portugal., Springer S; Constructor University, 28759, Bremen, Germany., Videira PA; Associate Laboratory i4HB, NOVA School of Science and Technology, Institute for Health and Bioeconomy, Universidade NOVA de Lisboa, 2829-516, Caparica, Portugal. p.videira@fct.unl.pt.; Department of Life Sciences, Applied Molecular Biosciences Unit, UCIBIO, NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2829-516, Caparica, Portugal. p.videira@fct.unl.pt.; Department of Life Sciences, CDG & Allies Professionals and Patient Associations International Network (CDG & Allies-PPAIN), NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2829-516, Caparica, Portugal. p.videira@fct.unl.pt.
Jazyk: angličtina
Zdroj: Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2024 Nov 02; Vol. 74 (1), pp. 9. Date of Electronic Publication: 2024 Nov 02.
DOI: 10.1007/s00262-024-03863-7
Abstrakt: Sialic acids at the cell surface of dendritic cells (DCs) play an important immunomodulatory role, and their manipulation enhances DC maturation, leading to heightened T cell activation. Particularly, at the molecular level, the increased stability of surface MHC-I molecules in monocyte-derived DCs (MoDCs) underpins an improved DC: T cell interaction. In this study, we focused on the impact of sialic acid remodelling by treatment with Clostridium perfringens sialidase on MoDCs' phenotypic and functional characteristics. Our investigation juxtaposes this novel approach with the conventional cytokine-based maturation regimen commonly employed in clinical settings.Notably, C. perfringens sialidase remarkably increased MHC-I levels compared to other sialidases having different specificities, supporting the idea that higher MHC-I is due to the cleavage of specific sialoglycans on cell surface proteins. Sialidase treatment induced rapid elevated surface expression of MHC-I, MHC-II and CD40 within an hour, a response not fully replicated by 48 h cytokine cocktail treatment. These increases were also observable 48 h post sialidase treatment. While CD86 and PD-L1 showed significant increases after 48 h of cytokine maturation, 48 h post sialidase treatment showed a higher increase in CD86 and shorter increase in PD-L1. CCR-7 expression was significantly increased 48 h after sialidase treatment but not significantly affected by cytokine maturation. Both treatments promoted higher secretion of the IL-12 cytokine. However, the cytokine cocktail induced a more pronounced IL-12 production. SNA lectin staining analysis demonstrated that the sialic acid profile is significantly altered by sialidase treatment, but not by the cytokine cocktail, which causes only slight sialic acid upregulation. Notably, the lipid-presenting molecules CD1a, CD1b and CD1c remained unaffected by sialidase treatment in MoDCs, a finding also further supported by experiments performed on C1R cells. Inhibition of endogenous sialidases Neu1 and Neu3 during MoDC differentiation did not affect surface MHC-I expression and cytokine secretion. Yet, sialidase activity in MoDCs was minimal, suggesting that sialidase inhibition does not significantly alter MHC-I-related functions. Our study highlights the unique maturation profile induced by sialic acid manipulation in MoDCs. These findings provide insights into the potential of sialic acid manipulation as a rapid immunomodulatory strategy, offering promising avenues for targeted interventions in inflammatory contexts.
(© 2024. The Author(s).)
Databáze: MEDLINE
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