Stem Cells
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 QUICK SEARCH:   [advanced]


     


First published online October 25, 2007
Stem Cells Vol. 26 No. 1 January 2008, pp. 279 -289
doi:10.1634/stemcells.2007-0454; www.StemCells.com
© 2008 AlphaMed Press

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
2007-0454v1
26/1/279    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Reprints/Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Liotta, F.
Right arrow Articles by Annunziato, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Liotta, F.
Right arrow Articles by Annunziato, F.

TRANSLATIONAL AND CLINICAL RESEARCH

Toll-Like Receptors 3 and 4 Are Expressed by Human Bone Marrow-Derived Mesenchymal Stem Cells and Can Inhibit Their T-Cell Modulatory Activity by Impairing Notch Signaling

Francesco Liottaa, Roberta Angelia, Lorenzo Cosmia, Lucia Filìa, Cinzia Manuellia, Francesca Frosalia, Benedetta Mazzinghia, Laura Maggia, Annalisa Pasinib, Veronica Lisib, Veronica Santarlascia, Lara Consolonia, Maria Lucia Angelottia, Paola Romagnania, Paola Parronchia, Mauro Kramperab, Enrico Maggia, Sergio Romagnania, Francesco Annunziatoa

aExcellence Center of the University of Florence De Novo Therapy, Florence, Italy;
bSection of Haematology, Department of Clinical and Experimental Medicine, University of Verona, Verona, Italy

Key Words. Tolerance • Suppression • Anergy • Stem cells • T cells • Notch

Correspondence: Correspondence: Sergio Romagnani, Ph.D., Department of Internal Medicine, University of Florence, Viale Morgagni 85, Firenze 50134, Italy. Telephone: 39-055-413663; Fax: 39-055-4271500; e-mail: s.romagnani{at}dmi.unifi.it

Received on June 15, 2007; accepted for publication on October 15, 2007.

First published online in STEM CELLS EXPRESS  October 25, 2007.


Bone marrow (BM)-derived mesenchymal stem cells (MSCs) are multipotent, nonhemopoietic progenitors that also possess regulatory activity on immune effector cells through different mechanisms. We demonstrate that human BM-derived MSCs expressed high levels of Toll-like receptors (TLRs) 3 and 4, which are both functional, as shown by the ability of their ligands to induce nuclear factor {kappa}B (NF-{kappa}B) activity, as well as the production of interleukin (IL)-6, IL-8, and CXCL10. Of note, ligation of TLR3 and TLR4 on MSCs also inhibited the ability of these cells to suppress the proliferation of T cells, without influencing their immunophenotype or differentiation potential. The TLR triggering effects appeared to be related to the impairment of MSC signaling to Notch receptors in T cells. Indeed, MSCs expressed the Notch ligand Jagged-1, and TLR3 or TLR4 ligation resulted in its strong downregulation. Moreover, anti-Jagged-1 neutralizing antibody and N[N-(3,5-difluorophenacetyl-L-alanyl)]-S-phenylglycine t-butyl ester (DAPT), an inhibitor of Notch signaling, hampered the suppressive activity of MSCs on T-cell proliferation. These data suggest that TLR3 and TLR4 expression on MSCs may provide an effective mechanism to block the immunosuppressive activity of MSCs and therefore to restore an efficient T-cell response in the course of dangerous infections, such as those sustained by double-stranded RNA viruses or Gram-negative bacteria, respectively.

Disclosure of potential conflicts of interest is found at the end of this article.




This article has been cited by other articles:


Home page
Rheumatology (Oxford)Home page
C. Bouffi, F. Djouad, M. Mathieu, D. Noel, and C. Jorgensen
Multipotent mesenchymal stromal cells and rheumatoid arthritis: risk or benefit?
Rheumatology, June 26, 2009; (2009) kep162v1.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
R. Romieu-Mourez, M. Francois, M.-N. Boivin, M. Bouchentouf, D. E. Spaner, and J. Galipeau
Cytokine Modulation of TLR Expression and Activation in Mesenchymal Stromal Cells Leads to a Proinflammatory Phenotype
J. Immunol., June 15, 2009; 182(12): 7963 - 7973.
[Abstract] [Full Text] [PDF]


Home page
J. Leukoc. Biol.Home page
M. Sioud and Y. Floisand
NOD2/CARD15 on bone marrow CD34+ hematopoietic cells mediates induction of cytokines and cell differentiation
J. Leukoc. Biol., June 1, 2009; 85(6): 939 - 946.
[Abstract] [Full Text] [PDF]


Home page
Stem CellsHome page
C. A. Opitz, U. M. Litzenburger, C. Lutz, T. V. Lanz, I. Tritschler, A. Koppel, E. Tolosa, M. Hoberg, J. Anderl, W. K. Aicher, et al.
Toll-Like Receptor Engagement Enhances the Immunosuppressive Properties of Human Bone Marrow-Derived Mesenchymal Stem Cells by Inducing Indoleamine-2,3-dioxygenase-1 via Interferon-{beta} and Protein Kinase R
Stem Cells, April 1, 2009; 27(4): 909 - 919.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
STEM CELLS THE ONCOLOGIST CME ALPHAMED PRESS JOURNALS

Copyright © 2008 by AlphaMed Press.