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Interferon-γ Regulates the Proliferation and Differentiation of Mesenchymal Stem Cells via Activation of Indoleamine 2,3 Dioxygenase (IDO)

2011; Public Library of Science; Volume: 6; Issue: 2 Linguagem: Inglês

10.1371/journal.pone.0014698

1932-6203

Juliana Croitoru‐Lamoury, F. Lamoury, Michael Caristo, Kazuo Suzuki, David W. Walker, Osamu Takikawa, Rosanne M. Taylor, Bruce J. Brew,

Neuroinflammation and Neurodegeneration Mechanisms

The kynurenine pathway (KP) of tryptophan metabolism is linked to antimicrobial activity and modulation of immune responses but its role in stem cell biology is unknown. We show that human and mouse mesenchymal and neural stem cells (MSCs and NSCs) express the complete KP, including indoleamine 2,3 dioxygenase 1 (IDO) and IDO2, that it is highly regulated by type I (IFN-β) and II interferons (IFN-γ), and that its transcriptional modulation depends on the type of interferon, cell type and species. IFN-γ inhibited proliferation and altered human and mouse MSC neural, adipocytic and osteocytic differentiation via the activation of IDO. A functional KP present in MSCs, NSCs and perhaps other stem cell types offers novel therapeutic opportunities for optimisation of stem cell proliferation and differentiation.