Mesenchymal Stem Cells Inhibit The Differentiation Of Dendritic Cells Through An Il-6-Dependent Mechanism

¹ Inserm, U 844, MONTPELLIER, F-34197 France; Université MONTPELLIER1, UFR de Médecine, Montpellier, F-34000 France
² Inserm; U 844, MONTPELLIER, F-34197 France; Université MONTPELLIER1, UFR de Médecine, Montpellier, F-34000 France; CHU Montpellier, Hôpital Lapeyronie, Unité Clinique d'Immuno-Rhumatologie, Montpellier, F-34295 France

^* To whom correspondence should be addressed. E-mail: noel{at}montp.inserm.fr.

	Abstract

Mesenchymal stem cells (MSCs) are of particular interest for their potential clinical use in tissue engineering as well as for their capacity to reduce the incidence and severity of graft-versus-host disease in allogeneic transplantation. We have previously shown that MSC-mediated immune suppression acts via the secretion of soluble factor(s) induced upon stimulation. The aim of this study was to identify the molecule(s) involved and the underlying mechanism(s). We show that murine MSC secrete high levels of IL-6 and VEGF which are directly correlated to the inhibition of T cell proliferation. The T cell activation is partially restored upon addition of a neutralizing anti-IL-6 antibody or the PGE2 inhibitor indomethacin. Interestingly, no indoleamine 2,3-dioxygenase activity was detected in our conditions. Instead, we show that MSC reduce the expression of MHC class II, CD40 and CD86 costimulatory molecules on mature dendritic cells (DC) which was responsible for a decrease of T cell proliferation. Moreover, we show that the differentiation of bone marrow progenitors into DC cultured with conditioned supernatants from MSC was partly inhibited through the secretion of IL-6. Altogether, these data suggest that IL-6 is involved in the immunoregulatory mechanism mediated by MSC through a partial inhibition of DC differentiation but is probably not the main mechanism.

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