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 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.

Characterization of Dental Pulp Stem Cells Response to Bone Substitutes Biomaterials in Dentistry

“…Human DPSCs were isolated from third molars of adult subjects ( n = 3; 30 to 35 years old) during routine extraction procedures, after obtaining their written informed consent in compliance with the Declaration of Helsinki. Cells were isolated from dental pulp, as previously described by Di Tinco et al (2021) [ 24 ]. Briefly, after the extraction of the dental pulp, it was harvested from the teeth and underwent enzymatic digestion using a digestive solution (3 mg/mL type I collagenase, plus 4 mg/mL dispase in α-MEM).…”

“…Human peripheral blood was collected from healthy donors ( n = 5) who gave written informed consent, according to the guidelines of the ethics committee. Peripheral blood mononuclear cells (PBMCs) were isolated using Histopaque (Sigma-Aldrich, Saint Louis, MO, USA), according to the manufacturer’ instructions, and pre-activated as previously described [ 24 ]. In particular, direct co-culture systems were established by seeding hDPSCs at a cell density of 5000 cells/cm 2 , and cultured in RPMI 1640 medium supplemented with 10% FBS, 2 mM glutamine, 100 units/mL penicillin, and 100 mg/mL streptomycin.…”

“…Confocal imaging was performed using a Nikon A1 confocal laser scanning microscope. The confocal serial sections were processed with ImageJ software to obtain 3-dimensional projections, and image rendering was performed by Adobe Photoshop Software [ 24 ].…”

Syngeneically transplanted insulin producing cells differentiated from adipose derived stem cells undergo delayed damage by autoimmune responses in NOD mice

“…Furthermore, the involvement in T1DM of programmed cell death ligand 1 (PD-L1), a well-known immune checkpoint, has been reported 16 . PD-L1 plays a major role in suppressing acquired immunity in autoimmune diseases, allogeneic transplantation and a stem cell experiment 17 . We have focused on the expression of PD-L1 in our IPCs, and found that PD-L1 expression may limit the effect of autoimmunity in IPCs 9 .…”

Stem Cells: A Promising Therapeutic Target for COVID-19

“…DPSCs have been shown to be efficient as a potential therapy for severe COVID-19 and they have shown a great curative potential despite the lack of a full understanding of the mechanisms [22] [23]. DPSCs hold promising immunomodulatory potential that might enhance their medical use in infectious diseases and inflammation [24].…”