Human mesenchymal stem cells target adhesion molecules and receptors involved in T cell extravasation

Federica Benvenuto, Adriana Voci, Enrico Carminati, Francesca Gualandi, Gianluigi Mancardi, Antonio Uccelli, Laura Vergani

Research output: Contribution to journalArticle

Abstract

Introduction: Systemic delivery of bone marrow-derived mesenchymal stem cells (MSC) seems to be of benefit in the treatment of multiple sclerosis (MS), an autoimmune disease of the central nervous system (CNS) sustained by migration of T cells across the brain blood barrier (BBB) and subsequent induction of inflammatory lesions into CNS. MSC have been found to modulate several effector functions of T cells. In this study, we investigated the effects of MSC on adhesion molecules and receptors on T cell surface that sustain their transendothelial migration. Methods: We used different co-culture methods combined with real-time PCR and flow cytometry to evaluate the expression both at the mRNA and at the plasma-membrane level of α4 integrin, β2 integrin, ICAM-1 and CXCR3. In parallel, we assessed if MSC are able to modulate expression of adhesion molecules on the endothelial cells that interact with T cells during their transendothelial migration. Results: Our in vitro analyses revealed that MSC: (i) inhibit proliferation and activation of both peripheral blood mononuclear cells (PBMC) and CD3+-selected lymphocytes through the release of soluble factors; (ii) exert suppressive effects on those surface molecules highly expressed by activated lymphocytes and involved in transendothelial migration; (iii) inhibit CXCL10-driven chemotaxis of CD3+ cells; (iv) down-regulated expression of adhesion molecules on endothelial cells. Conclusions: Taken together, these data demonstrate that the immunosuppressive effect of MSC does not exclusively depends on their anti-proliferative activity on T cells, but also on the impairment of leukocyte migratory potential through the inhibition of the adhesion molecules and receptors that are responsible for T cell trafficking across BBB. This could suggest a new mechanism through which MSC modulate T cell responses.

Original languageEnglish
Article number222
JournalStem Cell Research and Therapy
Volume6
Issue number1
DOIs
Publication statusPublished - Dec 10 2015

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Keywords

  • CD3-selected lymphocytes
  • human endothelial cells
  • immunosuppressive effects
  • leukocyte migratory potential
  • mesenchymal stem cells
  • surface adhesion molecules and receptors
  • transendothelial migration

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Molecular Medicine
  • Cell Biology
  • Medicine (miscellaneous)

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