Departmental Papers (Dental)

Document Type

Journal Article

Date of this Version

11-2011

Publication Source

Stem Cells

Volume

29

Issue

11

Start Page

1849

Last Page

1860

DOI

10.1002/stem.738

Abstract

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.

Comments

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.

Keywords

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

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Date Posted: 10 February 2023

This document has been peer reviewed.