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

Abstract 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 m...

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Autores principales:	Rosanna Di Tinco, Giulia Bertani, Alessandra Pisciotta, Laura Bertoni, Elisa Pignatti, Monia Maccaferri, Jessika Bertacchini, Paola Sena, Antonio Vallarola, Rossella Tupler, Stefania Croci, Martina Bonacini, Carlo Salvarani, Gianluca Carnevale
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	DPSCs Immunomodulatory functions PD1/PD-L1 pathway Neural crest stem cells Medicine (General) R5-920 Biochemistry QD415-436
Acceso en línea:	https://doaj.org/article/1eed0fe5184442daa59e15a07f4b4124
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spelling	oai:doaj.org-article:1eed0fe5184442daa59e15a07f4b41242021-12-05T12:05:46ZRole of PD-L1 in licensing immunoregulatory function of dental pulp mesenchymal stem cells10.1186/s13287-021-02664-41757-6512https://doaj.org/article/1eed0fe5184442daa59e15a07f4b41242021-12-01T00:00:00Zhttps://doi.org/10.1186/s13287-021-02664-4https://doaj.org/toc/1757-6512Abstract 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.Rosanna Di TincoGiulia BertaniAlessandra PisciottaLaura BertoniElisa PignattiMonia MaccaferriJessika BertacchiniPaola SenaAntonio VallarolaRossella TuplerStefania CrociMartina BonaciniCarlo SalvaraniGianluca CarnevaleBMCarticleDPSCsImmunomodulatory functionsPD1/PD-L1 pathwayNeural crest stem cellsMedicine (General)R5-920BiochemistryQD415-436ENStem Cell Research & Therapy, Vol 12, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	DPSCs Immunomodulatory functions PD1/PD-L1 pathway Neural crest stem cells Medicine (General) R5-920 Biochemistry QD415-436
spellingShingle	DPSCs Immunomodulatory functions PD1/PD-L1 pathway Neural crest stem cells Medicine (General) R5-920 Biochemistry QD415-436 Rosanna Di Tinco Giulia Bertani Alessandra Pisciotta Laura Bertoni Elisa Pignatti Monia Maccaferri Jessika Bertacchini Paola Sena Antonio Vallarola Rossella Tupler Stefania Croci Martina Bonacini Carlo Salvarani Gianluca Carnevale Role of PD-L1 in licensing immunoregulatory function of dental pulp mesenchymal stem cells
description	Abstract 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.
format	article
author	Rosanna Di Tinco Giulia Bertani Alessandra Pisciotta Laura Bertoni Elisa Pignatti Monia Maccaferri Jessika Bertacchini Paola Sena Antonio Vallarola Rossella Tupler Stefania Croci Martina Bonacini Carlo Salvarani Gianluca Carnevale
author_facet	Rosanna Di Tinco Giulia Bertani Alessandra Pisciotta Laura Bertoni Elisa Pignatti Monia Maccaferri Jessika Bertacchini Paola Sena Antonio Vallarola Rossella Tupler Stefania Croci Martina Bonacini Carlo Salvarani Gianluca Carnevale
author_sort	Rosanna Di Tinco
title	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_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_sort	role of pd-l1 in licensing immunoregulatory function of dental pulp mesenchymal stem cells
publisher	BMC
publishDate	2021
url	https://doaj.org/article/1eed0fe5184442daa59e15a07f4b4124
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Role of PD-L1 in licensing immunoregulatory function of dental pulp mesenchymal stem cells

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