Galectin-1 and semaphorin-3A are two soluble factors conferring T-cell immunosuppression to bone marrow mesenchymal stem cell.
In human physiology and animal models, bone marrow mesenchymal stem cells (MSCs) exert an immunosuppressive role in both in vitro and in vivo experiments. However, cellular and molecular mechanisms involved in this process are not clear and remain largely elusive. Several studies have suggested the implication of cell-cell contacts or soluble factors including transforming growth factor-b1 (TGF-b1), interleukin-10 (IL-10), indoleamine 2,3-dioxygenase (IDO), or human leukocyte antigen-G (HLA-G). Here, we show that both Galectin-1 and Semaphorin-3A (Sema-3A), 2 soluble factors capable to inhibit T-cell proliferation through neuropilin-1 (NP-1) binding, are highly expressed by MSCs and may account for their known suppressive activities. Furthermore, MSCs suppressive functions are completely reverted by soluble recombinant NP-1, the main receptor of both Galectin-1 and Sema-3A. Similar results were obtained by using blocking antibodies against Galectin-1 or Sema-3A. Taken together, these results demonstrate the critical role of Galectin-1 and Sema-3A in MSCs functions and may open new perspectives in the understanding and treatment of various immune and neoplastic disorders.
Lepelletier
Yves
Y
CNRS UMR 8147, Université Paris Descartes , Hôpital Necker, Paris, France.
Lecourt
Séverine
S
Renand
Amédée
A
Arnulf
Bertrand
B
Vanneaux
Valérie
V
Fermand
Jean-Paul
JP
Menasché
Philippe
P
Domet
Thomas
T
Marolleau
Jean-Pierre
JP
Hermine
Olivier
O
Larghero
Jérôme
J
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology*; D049109:Cell Proliferation; D037483:Galectin 1 / Q000276:immunology*; D006801:Humans; D007165:Immunosuppression Therapy; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology*; D040121:Semaphorin-3A / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D015415:Biomarkers; D037483:Galectin 1; D040121:Semaphorin-3A