Departmental Papers (Dental)
Human Gingiva-Derived Mesenchymal Stromal Cells Attenuate Contact Hypersensitivity via Prostaglandin E2- Dependent Mechanisms
Date of this Version
The 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 hypersensitivity, Human gingival, Immunomodulation, Mast cells, Stromal cells MeSH: Animals, Cells, Cultured, Dermatitis, Contact, Dinoprostone, Flow Cytometry, Gingiva, Humans, Mesenchymal Stromal Cells, Mice EMTREE drug terms: interleukin 10, prostaglandin E2, tumor necrosis factor alpha EMTREE medical terms: animal experiment, animal model, animal tissue, article, CD8+ T lymphocyte, cell differentiation, cell interaction, contact allergy, controlled study, dendritic cell, desensitization, gingiva derived mesenchymal stromal cell, human, human cell, human tissue, immunomodulation, intracellular signaling, lymph node, lymphocytic infiltration, male, mast cell, mesenchymal stem cell, mouse, nonhuman, protein expression, regulatory T lymphocyte, stroma cell, Th17 cell
Su, W., Zhang, Q., Shi, S., Nguyen, A. L., & Le, A. D. (2011). Human Gingiva-Derived Mesenchymal Stromal Cells Attenuate Contact Hypersensitivity via Prostaglandin E2- Dependent Mechanisms. Stem Cells, 29 (11), 1849-1860. http://dx.doi.org/10.1002/stem.738
Endodontics and Endodontology Commons, Oral and Maxillofacial Surgery Commons, Oral Biology and Oral Pathology Commons
Date Posted: 10 February 2023
This document has been peer reviewed.
At the time of publication, author Qun-Zhou Zhang was affiliated with the University of Southern California. Currently, (s)he is a faculty member at the School of Dental Medicine at the University of Pennsylvania.
At the time of publication, author Shihong Shi was affiliated with the University of Southern California. Currently, (s)he is a faculty member at the School of Dental Medicine at the University of Pennsylvania.
At the time of publication, author Anh D. Le was affiliated with the University of Southern California. Currently, (s)he is a faculty member at the School of Dental Medicine at the University of Pennsylvania.