Tumor necrosis factor α, agonist and antagonists of cannabinoid receptor type 1 and type 2 alter the immunephenotype of stem cells from human exfoliated deciduous teeth

Abstract The endocannabinoid system (ECS) is composed of endocannabinoid molecules synthesizing and degrading ligands and cannabinoid receptors such as types CB1 and CB2. The ECS is present in various tissues and cell types, such as in central nervous system, immune system, and mesenchymal stem cells. The presence of these receptors in both immune system cells and stem cells shows a common pathway of communication-related to repair and immunomodulation. The aim of the present study was to verify the participation of ECS in the immunomodulatory profile of stem cells from human exfoliated deciduous teeth (SHED), in the presence or absence of TNF-α. SHED was cultured in the presence or absence of the agonist anandamide and the two antagonists AM251 and SR144528 of CB1 and CB2 receptors, under stimulation or not of TNF-α. For immunomodulation analysis, surface molecules linked to immunomodulation: HLA-DR, PD-L1 and PD-L2 were measured by flow cytometry. The results showed that SHED respond to ECS and TNF-α by altering key molecules of the immune response. It is concluded that the inhibition of endocannabinoid receptors added with the pro-inflammatory effect of TNF-α led SHED to show increased HLA-DR, as well as, to assume an anti-inflammatory profile by increasing PD-L1 and PD-L2.