Immunomodulatory properties of human dental pulp stromal cells: the role of IL-6/JAK/STAT3 pathway and PD-L1

Human Dental Pulp Stromal Cells (hDPSCs) of neural-ectodermal origin hold immunomodulatory properties which make them a source for MSC-based therapies for the treatment of autoimmune diseases. Our results highlighted that hDPSCs exposed to different inflammatory conditions activate Fas/FasL and PD1/PD-L1 pathways. Moreover, hDPSCs modulate inflammatory cytokines release of aPBMCs from Rheumatoid Arthritis (RA) patients. However, the inflammatory milieu induced the upregulation of IL-6 by hDPSCs, which was demonstrated to be strongly correlated to PD-L1 expression, suggesting its involvement in supporting their immunoregulation. Our data demonstrated that the activation of the IL6/JAK/STAT3 trans-signaling pathway in hDPSCs through stimulation with the IL6/sIL6R complex leads to an increase in PD-L1 protein levels, but not PD-L2, via proteasome inhibition. The activation of the IL-6/PD-L1 axis in response to inflammatory conditions underscores its potential significance in autoimmune diseases since a dysfunction of this mechanism could lead to the onset and progression of chronic inflammatory disorders.