Departmental Papers (Dental)

Document Type

Journal Article

Date of this Version

3-1-2010

Publication Source

Journal of Immunology

Volume

184

Issue

5

Start Page

2321

Last Page

2328

DOI

10.4049/jimmunol.0902023

Abstract

Cell-cell adhesion mediated by ICAM-1 and VCAM-1 is critical for T cell activation and leukocyte recruitment to the inflammation site and, therefore, plays an important role in evoking effective immune responses. However, we found that ICAM-1 and VCAM-1 were critical for mesenchymal stem cell (MSC)-mediated immunosuppression. When MSCs were cocultured with T cells in the presence of T cell Ag receptor activation, they significantly upregulated the adhesive capability of T cells due to the increased expression of ICAM-1 and VCAM-1. By comparing the immunosuppressive effect of MSCs toward various subtypes of T cells and the expression of these adhesion molecules, we found that the greater expression of ICAM-1 and VCAM-1 by MSCs, the greater the immunosuppressive capacity that they exhibited. Furthermore, ICAM-1 and VCAM-1 were found to be inducible by the concomitant presence of IFN-γ and inflammatory cytokines (TNF-α or IL-1). Finally, MSC-mediated immunosuppression was significantly reversed in vitro and in vivo when the adhesion molecules were genetically deleted or functionally blocked, which corroborated the importance of cell-cell contact in immunosuppression by MSCs. Taken together, these findings reveal a novel function of adhesion molecules in immunoregulation by MSCs and provide new insights for the clinical studies of antiadhesion therapies in various immune disorders. Copyright © 2010 by The American Association of Immunologists, Inc.

Comments

At the time of publication, author Anh D. Le was affiliated with the University of Southern California, School of Dentistry. Currently, (s)he is a faculty member at the School of Dental Medicine at the University of Pennsylvania.

At the time of publication, author Songtao Shi was affiliated with the University of Southern California, School of Dentistry. Currently, (s)he is a faculty member at the School of Dental Medicine at the University of Pennsylvania.

Keywords

MeSH: Animals, Antibodies, Neutralizing, Cells, Cultured, Coculture Techniques, Culture Media, Conditioned, Female, Flow Cytometry, Immunosuppression, Inflammation Mediators, Intercellular Adhesion Molecule-1, Interferon-gamma, Interleukin-1, Male, Mesenchymal Stem Cells, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Receptors, Interferon, Receptors, Tumor Necrosis Factor, Type I, Reverse Transcriptase Polymerase Chain Reaction, Spleen, T-Lymphocytes, Tumor Necrosis Factor-alpha, Vascular Cell Adhesion Molecule-1 EMTREE drug terms: cytokine, gamma interferon, intercellular adhesion molecule 1, interleukin 1, T lymphocyte receptor, tumor necrosis factor alpha, vascular cell adhesion molecule 1, autacoid, gamma interferon, gamma interferon receptor, intercellular adhesion molecule 1, interferon receptor, interleukin 1, neutralizing antibody, tumor necrosis factor alpha, tumor necrosis factor receptor 1, vascular cell adhesion molecule 1 EMTREE medical terms: animal cell, animal experiment, animal tissue, article, cell adhesion, cell interaction, coculture, controlled study, enzyme activation, female, gene deletion, gene function, immunoregulation, immunosuppressive treatment, in vitro study, in vivo study, mesenchymal stem cell, mouse, nonhuman, priority journal, protein expression, T lymphocyte, upregulation, animal, C57BL mouse, cell culture, culture medium, cytology, drug effect, flow cytometry, genetics, immunology, immunosuppressive treatment, male, metabolism, mouse mutant, reverse transcription polymerase chain reaction, spleen, transgenic mouse

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Date Posted: 10 February 2023

This document has been peer reviewed.