title: Human mesenchymal stem cells target adhesion molecules and receptors involved in T cell extravasation.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, IRCCS-AUO San Martino-IST, Largo Paolo Daneo 3, 16132, Genova, Italy. febenvenuto@yahoo.it.|Centre of Excellence for Biomedical Research (CEBR), University of Genoa, Viale Benedetto XV 7, 16132, Genova, Italy. febenvenuto@yahoo.it.
authors.forename: Federica
authors.initials: F
authors.lastname: Benvenuto
authors.affiliation: Department of Earth, Environment and Life Sciences (DISTAV), University of Genoa, Corso Europa 26, 16132, Genova, Italy. Adriana.Voci@unige.it.
authors.forename: Adriana
authors.initials: A
authors.lastname: Voci
authors.affiliation: Department of Earth, Environment and Life Sciences (DISTAV), University of Genoa, Corso Europa 26, 16132, Genova, Italy. enrico.carminati84@gmail.com.
authors.forename: Enrico
authors.initials: E
authors.lastname: Carminati
authors.affiliation: Division of Hematology and Bone Marrow Transplant Unit, IRCCS-AUO San Martino-IST, Largo Rosanna Benzi 10, 16132, Genova, Italy. francesca.gualandi@hsanmartino.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Gualandi
authors.affiliation: Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, IRCCS-AUO San Martino-IST, Largo Paolo Daneo 3, 16132, Genova, Italy. glmancardi@neurologia.unige.it.|Centre of Excellence for Biomedical Research (CEBR), University of Genoa, Viale Benedetto XV 7, 16132, Genova, Italy. glmancardi@neurologia.unige.it.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Mancardi
authors.affiliation: Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, IRCCS-AUO San Martino-IST, Largo Paolo Daneo 3, 16132, Genova, Italy. auccelli@neurologia.unige.it.|Centre of Excellence for Biomedical Research (CEBR), University of Genoa, Viale Benedetto XV 7, 16132, Genova, Italy. auccelli@neurologia.unige.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Uccelli
authors.affiliation: Department of Earth, Environment and Life Sciences (DISTAV), University of Genoa, Corso Europa 26, 16132, Genova, Italy. Laura.Vergani@unige.it.
authors.forename: Laura
authors.initials: L
authors.lastname: Vergani
mesh_terms: D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000276:immunology; D049109:Cell Proliferation; D054357:Chemokine CXCL10 / Q000378:metabolism; D002634:Chemotaxis, Leukocyte; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000166:cytology / Q000276:immunology; D015870:Gene Expression; D006801:Humans; D007165:Immunosuppression Therapy; D008213:Lymphocyte Activation; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology / Q000628:therapy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054367:Receptors, CXCR3 / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
chemical_list: C114753:CXCL10 protein, human; C515187:CXCR3 protein, human; D015815:Cell Adhesion Molecules; D054357:Chemokine CXCL10; D012333:RNA, Messenger; D054367:Receptors, CXCR3