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Interferon-? regulates the proliferation and differentiation of mesenchymal stem cells via activation of indoleamine 2,3 dioxygenase (IDO).

ABSTRACT: 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-?) and II interferons (IFN-?), and that its transcriptional modulation depends on the type of interferon, cell type and species. IFN-? 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.

SUBMITTER: Croitoru-Lamoury J 

PROVIDER: S-EPMC3040184 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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Interferon-γ regulates the proliferation and differentiation of mesenchymal stem cells via activation of indoleamine 2,3 dioxygenase (IDO).

Croitoru-Lamoury Juliana J   Lamoury Francois M J FM   Caristo Michael M   Suzuki Kazuo K   Walker David D   Takikawa Osamu O   Taylor Rosanne R   Brew Bruce J BJ  

PloS one 20110216 2

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  ...[more]

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