Su, Wen-RuZhang, Qun-ZhouShi, Shi-HongNguyen, Andrew LLe, Anh D2023-05-222023-05-222011-11-012022-06-16https://repository.upenn.edu/handle/20.500.14332/9284The immunomodulatory and anti-inflammatory functions of mesenchymal stromal cells (MSCs) have been demonstrated in several autoimmune/inflammatory disease models, but their contribution to the mitigation of contact hypersensitivity (CHS) remains unclear. Here, we report a new immunological approach using human gingiva-derived MSCs (GMSCs) to desensitize and suppress CHS and the underlying mechanisms. Our results showed that systemic infusion of GMSCs before the sensitization and challenge phase dramatically suppress CHS, manifested as a decreased infiltration of dendritic cells (DCs), CD8 + T cells, T H-17 and mast cells (MCs), a suppression of a variety of inflammatory cytokines, and a reciprocal increased infiltration of regulatory T cells and expression of IL-10 at the regional lymph nodes and the allergic contact areas. The GMSC-mediated immunosuppressive effects and mitigation of CHS were significantly abrogated on pretreatment with indomethacin, an inhibitor of cyclooxygenases. Under coculture condition of direct cell-cell contact or via transwell system, GMSCs were capable of direct suppression of differentiation of DCs and phorbol 12-myristate 13-acetate-stimulated activation of MCs, whereas the inhibitory effects were attenuated by indomethacin. Mechanistically, GMSC-induced blockage of de novo synthesis of proinflammatory cytokines by MCs is mediated partly by the tumor necrosis factor-alpha/prostaglandin E 2 (PGE 2) feedback axis. These results demonstrate that GMSCs are capable of desensitizing allergic contact dermatitis via PGE 2-dependent mechanisms. © AlphaMed Press.Author keywords: Contact hypersensitivityHuman gingivalImmunomodulationMast cellsStromal cells MeSH: AnimalsCellsCulturedDermatitisContactDinoprostoneFlow CytometryGingivaHumansMesenchymal Stromal CellsMice EMTREE drug terms: interleukin 10prostaglandin E2tumor necrosis factor alpha EMTREE medical terms: animal experimentanimal modelanimal tissuearticleCD8+ T lymphocytecell differentiationcell interactioncontact allergycontrolled studydendritic celldesensitizationgingiva derived mesenchymal stromal cellhumanhuman cellhuman tissueimmunomodulationintracellular signalinglymph nodelymphocytic infiltrationmalemast cellmesenchymal stem cellmousenonhumanprotein expressionregulatory T lymphocytestroma cellTh17 cellDentistryEndodontics and EndodontologyOral and Maxillofacial SurgeryOral Biology and Oral PathologyArticle