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

Stem Cell Research & Therapy

Laura Vergani²  Antonio Uccelli¹  Gianluigi Mancardi¹  Francesca Gualandi³  Enrico Carminati²  Adriana Voci²  Federica Benvenuto¹ 

[1] Centre of Excellence for Biomedical Research (CEBR), University of Genoa, Viale Benedetto XV 7, Genova, 16132, Italy;Department of Earth, Environment and Life Sciences (DISTAV), University of Genoa, Corso Europa 26, Genova, 16132, Italy;Division of Hematology and Bone Marrow Transplant Unit, IRCCS-AUO San Martino-IST, Largo Rosanna Benzi 10, Genova, 16132, Italy

关键词: leukocyte migratory potential;    transendothelial migration;    surface adhesion molecules and receptors;    immunosuppressive effects;    human endothelial cells;    CD3+-selected lymphocytes;    mesenchymal stem cells;   

Others  :  1235609
DOI  :  10.1186/s13287-015-0222-y

 received in 2015-09-09, accepted in 2015-11-02,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Benvenuto et al.

【 图 表 】

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