TY - JOUR
T1 - A role for heme oxygenase-1 in the immunosuppressive effect of adult rat and human mesenchymal stem cells
AU - Chabannes, Dominique
AU - Hill, Marcelo
AU - Merieau, Emmanuel
AU - Rossignol, Julien
AU - Brion, Régis
AU - Soulillou, Jean Paul
AU - Anegon, Ignacio
AU - Cuturi, Maria Cristina
PY - 2007/11/15
Y1 - 2007/11/15
N2 - Mesenchymal stem cells (MSCs) display immunomodulatory properties mediated by various factors, including inducible nitric oxide synthase (iNOS). Since heme oxygenase-1 (HO-1) is a potent immunosuppressive enzyme, we tested the hypothesis that HO-1 could mediate the immunosuppressive effects of MSCs. We generated adult rat MSCs that inhibited T-cell proliferation in vitro. These MSCs expressed both HO-1 and iNOS. In vitro, whereas neither HO-1 nor iNOS inhibition alone could interfere with the immunosuppressive properties of rat MSCs, simultaneous inhibition of both enzymes restored T-cell proliferation. In vivo, injection of MSCs significantly delayed heart allograft rejection, and inhibition of either HO-1 or iNOS totally reversed the protective activity of MSCs, inducing rejection. Adult human MSCs also expressed HO-1; in these cells, HO-1 inhibition was sufficient to completely block their immunosuppressive capacity. In conclusion, we show, for the first time, that HO-1 mediates the immunosuppressive properties of rat and human MSCs.
AB - Mesenchymal stem cells (MSCs) display immunomodulatory properties mediated by various factors, including inducible nitric oxide synthase (iNOS). Since heme oxygenase-1 (HO-1) is a potent immunosuppressive enzyme, we tested the hypothesis that HO-1 could mediate the immunosuppressive effects of MSCs. We generated adult rat MSCs that inhibited T-cell proliferation in vitro. These MSCs expressed both HO-1 and iNOS. In vitro, whereas neither HO-1 nor iNOS inhibition alone could interfere with the immunosuppressive properties of rat MSCs, simultaneous inhibition of both enzymes restored T-cell proliferation. In vivo, injection of MSCs significantly delayed heart allograft rejection, and inhibition of either HO-1 or iNOS totally reversed the protective activity of MSCs, inducing rejection. Adult human MSCs also expressed HO-1; in these cells, HO-1 inhibition was sufficient to completely block their immunosuppressive capacity. In conclusion, we show, for the first time, that HO-1 mediates the immunosuppressive properties of rat and human MSCs.
UR - http://www.scopus.com/inward/record.url?scp=36349017810&partnerID=8YFLogxK
U2 - 10.1182/blood-2007-02-075481
DO - 10.1182/blood-2007-02-075481
M3 - Article
C2 - 17684157
AN - SCOPUS:36349017810
SN - 0006-4971
VL - 110
SP - 3691
EP - 3694
JO - Blood
JF - Blood
IS - 10
ER -