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Role of PD-L1 in licensing immunoregulatory function of dental pulp mesenchymal stem cells

BACKGROUND: Dental pulp stem cells (DPSCs) are low immunogenic and hold immunomodulatory properties that, along with their well-established multi-potency, might enhance their potential application in autoimmune and inflammatory diseases. The present study focused on the ability of DPSCs to modulate...

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Autores principales: Di Tinco, Rosanna, Bertani, Giulia, Pisciotta, Alessandra, Bertoni, Laura, Pignatti, Elisa, Maccaferri, Monia, Bertacchini, Jessika, Sena, Paola, Vallarola, Antonio, Tupler, Rossella, Croci, Stefania, Bonacini, Martina, Salvarani, Carlo, Carnevale, Gianluca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8643194/
https://www.ncbi.nlm.nih.gov/pubmed/34863286
http://dx.doi.org/10.1186/s13287-021-02664-4
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author Di Tinco, Rosanna
Bertani, Giulia
Pisciotta, Alessandra
Bertoni, Laura
Pignatti, Elisa
Maccaferri, Monia
Bertacchini, Jessika
Sena, Paola
Vallarola, Antonio
Tupler, Rossella
Croci, Stefania
Bonacini, Martina
Salvarani, Carlo
Carnevale, Gianluca
author_facet Di Tinco, Rosanna
Bertani, Giulia
Pisciotta, Alessandra
Bertoni, Laura
Pignatti, Elisa
Maccaferri, Monia
Bertacchini, Jessika
Sena, Paola
Vallarola, Antonio
Tupler, Rossella
Croci, Stefania
Bonacini, Martina
Salvarani, Carlo
Carnevale, Gianluca
author_sort Di Tinco, Rosanna
collection PubMed
description BACKGROUND: Dental pulp stem cells (DPSCs) are low immunogenic and hold immunomodulatory properties that, along with their well-established multi-potency, might enhance their potential application in autoimmune and inflammatory diseases. The present study focused on the ability of DPSCs to modulate the inflammatory microenvironment through PD1/PD-L1 pathway. METHODS: Inflammatory microenvironment was created in vitro by the activation of T cells isolated from healthy donors and rheumatoid arthritis (RA) patients with anti-CD3 and anti-CD28 antibodies. Direct and indirect co-cultures between DPSCs and PBMCs were carried out to evaluate the activation of immunomodulatory checkpoints in DPSCs and the inflammatory pattern in PBMCs. RESULTS: Our data suggest that the inflammatory stimuli trigger DPSCs immunoregulatory functions that can be exerted by both direct and indirect contact. As demonstrated by using a selective PD-L1 inhibitor, DPSCs were able to activate compensatory pathways targeting to orchestrate the inflammatory process by modulating pro-inflammatory cytokines in pre-activated T lymphocytes. The involvement of PD-L1 mechanism was also observed in autologous inflammatory status (pulpitis) and after direct exposure to pre-activated T cells from RA patients suggesting that immunomodulatory/anti-inflammatory properties are strictly related to their stemness status. CONCLUSIONS: Our findings point out that the communication with the inflammatory microenvironment is essential in licensing their immunomodulatory properties. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-021-02664-4.
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spelling pubmed-86431942021-12-06 Role of PD-L1 in licensing immunoregulatory function of dental pulp mesenchymal stem cells Di Tinco, Rosanna Bertani, Giulia Pisciotta, Alessandra Bertoni, Laura Pignatti, Elisa Maccaferri, Monia Bertacchini, Jessika Sena, Paola Vallarola, Antonio Tupler, Rossella Croci, Stefania Bonacini, Martina Salvarani, Carlo Carnevale, Gianluca Stem Cell Res Ther Research BACKGROUND: Dental pulp stem cells (DPSCs) are low immunogenic and hold immunomodulatory properties that, along with their well-established multi-potency, might enhance their potential application in autoimmune and inflammatory diseases. The present study focused on the ability of DPSCs to modulate the inflammatory microenvironment through PD1/PD-L1 pathway. METHODS: Inflammatory microenvironment was created in vitro by the activation of T cells isolated from healthy donors and rheumatoid arthritis (RA) patients with anti-CD3 and anti-CD28 antibodies. Direct and indirect co-cultures between DPSCs and PBMCs were carried out to evaluate the activation of immunomodulatory checkpoints in DPSCs and the inflammatory pattern in PBMCs. RESULTS: Our data suggest that the inflammatory stimuli trigger DPSCs immunoregulatory functions that can be exerted by both direct and indirect contact. As demonstrated by using a selective PD-L1 inhibitor, DPSCs were able to activate compensatory pathways targeting to orchestrate the inflammatory process by modulating pro-inflammatory cytokines in pre-activated T lymphocytes. The involvement of PD-L1 mechanism was also observed in autologous inflammatory status (pulpitis) and after direct exposure to pre-activated T cells from RA patients suggesting that immunomodulatory/anti-inflammatory properties are strictly related to their stemness status. CONCLUSIONS: Our findings point out that the communication with the inflammatory microenvironment is essential in licensing their immunomodulatory properties. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-021-02664-4. BioMed Central 2021-12-04 /pmc/articles/PMC8643194/ /pubmed/34863286 http://dx.doi.org/10.1186/s13287-021-02664-4 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Di Tinco, Rosanna
Bertani, Giulia
Pisciotta, Alessandra
Bertoni, Laura
Pignatti, Elisa
Maccaferri, Monia
Bertacchini, Jessika
Sena, Paola
Vallarola, Antonio
Tupler, Rossella
Croci, Stefania
Bonacini, Martina
Salvarani, Carlo
Carnevale, Gianluca
Role of PD-L1 in licensing immunoregulatory function of dental pulp mesenchymal stem cells
title Role of PD-L1 in licensing immunoregulatory function of dental pulp mesenchymal stem cells
title_full Role of PD-L1 in licensing immunoregulatory function of dental pulp mesenchymal stem cells
title_fullStr Role of PD-L1 in licensing immunoregulatory function of dental pulp mesenchymal stem cells
title_full_unstemmed Role of PD-L1 in licensing immunoregulatory function of dental pulp mesenchymal stem cells
title_short Role of PD-L1 in licensing immunoregulatory function of dental pulp mesenchymal stem cells
title_sort role of pd-l1 in licensing immunoregulatory function of dental pulp mesenchymal stem cells
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8643194/
https://www.ncbi.nlm.nih.gov/pubmed/34863286
http://dx.doi.org/10.1186/s13287-021-02664-4
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