Leukemia inhibitory factor: Role in human mesenchymal stem cells mediated immunosuppression.
The interactions between mesenchymal stem cells (MSCs) and immune system are currently being explored. Leukemia inhibitory factor (LIF) is linked to regulatory transplantation tolerance. Our aim was to study the expression of LIF on human MSCs at both gene and protein level in mixed lymphocyte reaction (MSC/MLR), and its implication in MSC immunosuppressive effect. There was a 7-fold increase (611pg/ml) in LIF in MSC/MLR as compared to MSCs alone. Using LIF neutralizing antibody, a significant restoration of up to 91% of CD3+ lymphocyte proliferation in MSC/MLR was observed (p=0.021). LIF was implicated in the generation of regulatory lymphocytes, as demonstrated by decrease of Foxp3+ regulatory cells after using LIF neutralizing antibody in MSC/MLR (p=0.06) by flow cytometry. A positive correlation between LIF and human leukocyte antigen (HLA-G) gene expression by MSCs was found (R(2)=0.74). Our findings provide evidence supporting the immunomodulatory effect of MSCs.
Nasef
Aisha
A
EA 1638 Laboratoire de Thérapie Cellulaire et Radioprotection Accidentelle (LTCRA), Faculté de médecine Saint Antoine, UPMC, Paris IV, 27 rue de Chaligny, 75012 Paris, France.
Mazurier
Christelle
C
Bouchet
Sandrine
S
François
Sabine
S
Chapel
Alain
A
Thierry
Dominique
D
Gorin
Norbert-Claude
NC
Fouillard
Loïc
L
D000906:Antibodies / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D002469:Cell Separation; D002478:Cells, Cultured; D051858:Forkhead Transcription Factors / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007165:Immunosuppression Therapy; D053605:Leukemia Inhibitory Factor / Q000276:immunology*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology*
D000906:Antibodies; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor