New insights into the immunomodulatory potential of sialic acid on monocyte-derived dendritic cells
Abstract 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-der...
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2024-11-01
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| Series: | Cancer Immunology, Immunotherapy |
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| Online Access: | https://doi.org/10.1007/s00262-024-03863-7 |
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| author | Zélia Silva João Amorim Rabaça Vanessa Luz Rita Adubeiro Lourenço Mariolina Salio Alexandra Couto Oliveira Pedro Bule Sebastian Springer Paula Alexandra Videira |
| author_facet | Zélia Silva João Amorim Rabaça Vanessa Luz Rita Adubeiro Lourenço Mariolina Salio Alexandra Couto Oliveira Pedro Bule Sebastian Springer Paula Alexandra Videira |
| author_sort | Zélia Silva |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-97151ab790fe44c2ad54acc084f71c72 |
| institution | Kabale University |
| issn | 1432-0851 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Springer |
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| series | Cancer Immunology, Immunotherapy |
| spelling | doaj-art-97151ab790fe44c2ad54acc084f71c722025-02-02T12:26:44ZengSpringerCancer Immunology, Immunotherapy1432-08512024-11-0174111310.1007/s00262-024-03863-7New insights into the immunomodulatory potential of sialic acid on monocyte-derived dendritic cellsZélia Silva0João Amorim Rabaça1Vanessa Luz2Rita Adubeiro Lourenço3Mariolina Salio4Alexandra Couto Oliveira5Pedro Bule6Sebastian Springer7Paula Alexandra Videira8Associate Laboratory i4HB, NOVA School of Science and Technology, Institute for Health and Bioeconomy, Universidade NOVA de LisboaAssociate Laboratory i4HB, NOVA School of Science and Technology, Institute for Health and Bioeconomy, Universidade NOVA de LisboaAssociate Laboratory i4HB, NOVA School of Science and Technology, Institute for Health and Bioeconomy, Universidade NOVA de LisboaAssociate Laboratory i4HB, NOVA School of Science and Technology, Institute for Health and Bioeconomy, Universidade NOVA de LisboaMedical Research Council Translational Immune Discovery Unit, Medical Research Council Weatherall Institute of Molecular Medicine, University of OxfordCIISA‑Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of LisbonCIISA‑Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of LisbonConstructor UniversityAssociate Laboratory i4HB, NOVA School of Science and Technology, Institute for Health and Bioeconomy, Universidade NOVA de LisboaAbstract 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.https://doi.org/10.1007/s00262-024-03863-7ImmunomodulationDendritic cellsSialic acidAntigen presentationMHC-I |
| spellingShingle | Zélia Silva João Amorim Rabaça Vanessa Luz Rita Adubeiro Lourenço Mariolina Salio Alexandra Couto Oliveira Pedro Bule Sebastian Springer Paula Alexandra Videira New insights into the immunomodulatory potential of sialic acid on monocyte-derived dendritic cells Cancer Immunology, Immunotherapy Immunomodulation Dendritic cells Sialic acid Antigen presentation MHC-I |
| title | New insights into the immunomodulatory potential of sialic acid on monocyte-derived dendritic cells |
| title_full | New insights into the immunomodulatory potential of sialic acid on monocyte-derived dendritic cells |
| title_fullStr | New insights into the immunomodulatory potential of sialic acid on monocyte-derived dendritic cells |
| title_full_unstemmed | New insights into the immunomodulatory potential of sialic acid on monocyte-derived dendritic cells |
| title_short | New insights into the immunomodulatory potential of sialic acid on monocyte-derived dendritic cells |
| title_sort | new insights into the immunomodulatory potential of sialic acid on monocyte derived dendritic cells |
| topic | Immunomodulation Dendritic cells Sialic acid Antigen presentation MHC-I |
| url | https://doi.org/10.1007/s00262-024-03863-7 |
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