DPSCs from inflamed pulp modulate macrophage function via the TNF-α/IDO axis

Human dental pulp stem cells (dpscs) can be isolated from inflamed pulp derived from carious teeth with symptomatic irreversible pulpitis (i-dpscs),which possess stemness and multidifferentiation potentials similar to dpscs from healthy pulp. since macrophages - essential cell players of the pulpal innate immunity - can regulate pulpal inflammation and repair,the authors investigated the immunomodulatory effects of dpscs/i-dpscs on macrophage functions and their underlying mechanisms. similar to dpscs,i-dpscs were capable of colony-forming efficiency and adipogenic and osteo/dentinogenic differentiation under in vitro induction conditions. i-dpscs also expressed a similar phenotypic profile of mesenchymal stem cell markers,except a relatively higher level of cd146 as compared with dpscs. coculture of dpscs or i-dpscs with differentiated thp-1 cells,the human monocyte cell line,markedly suppressed tumor necrosis factor α (tnf-α) secretion in response to stimulation with lipopolysaccharides (lps) and/or nigericin. however,unlike tnf-α,the secreted level of interleukin 1β was not affected by coculture with dpscs or i-dpscs. furthermore,dpsc/i-dpsc-mediated inhibition of tnf-α secretion by macrophages was abolished by pretreatment with 1-methyl-d-tryptophan,a specific inhibitor of indoleamine-pyrrole 2,3-dioxygenase (ido),but not by nsc-398,a specific inhibitor of cox-2,suggesting ido as a mediator. interestingly,ido expression was significantly augmented in macrophages and mesenchymal stromal cells in inflamed human pulp tissues. collectively,these findings show that i-dpscs,similar to dpscs,possess stem cell properties and suppress macrophage functions via the tnf-α/ido axis,thereby providing a physiologically relevant context for their innate immunomodulatory activity in the dental pulp and their capability for pulp repair. © international & american associations for dental research 2016.