Stem cells from exfoliated deciduous teeth transplantation ameliorates Sjögren's syndrome by secreting soluble PD-L1

Abstract

Mesenchymal stem cell transplantation (MSCT) regulates immune cells, and is a promising therapeutic approach for treating autoimmune diseases. Stem cells from human exfoliated deciduous teeth (SHED) are a unique postnatal stem cell population from the cranial neural crest with high self-renewal, multipotent differentiation, and superior immunomodulatory properties. However, the mechanisms by which SHED can treat autoimmune diseases remain unclear. Sjögren's syndrome (SS) is an autoimmune disease histologically characterized by high lymphocytic infiltration in the salivary and lacrimal glands that results in dryness symptoms. This study explores the potential of systemic transplantation of SHED to ameliorate SS-induced dryness symptoms in mice. Overall, SHED could rescue the balance of regulatory T cell (Treg)/T helper cell 17 (Th17) in the recipient SS mice. Mechanistically, SHED promoted Treg conversion and inhibited Th17 function via paracrine effects, which were related to the secretion of soluble programmed cell death ligand 1 (sPD-L1). Moreover, it directly induced Th17 apoptosis via cell-cell contact, leading to the up-regulation of Treg and down-regulation of Th17 cells. In summary, SHED-mediated rescue of Treg/Th17 balance via the sPD-L1/PD-1 pathway ameliorates the gland inflammation and dryness symptoms in SS mice. These findings suggest that SHED are a promising stem cell source for the treatment of autoimmune diseases in the clinical setting.