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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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Detalles Bibliográficos
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
Descripción
Sumario: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.