title: Interferon-γ 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-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.
authors.affiliation: St. Vincent's Centre for Applied Medical Research, St. Vincent's Hospital, Sydney, Australia. j.lamoury@amr.org.au
authors.forename: Juliana
authors.initials: J
authors.lastname: Croitoru-Lamoury
authors.forename: Francois M J
authors.initials: FM
authors.lastname: Lamoury
authors.forename: Michael
authors.initials: M
authors.lastname: Caristo
authors.forename: Kazuo
authors.initials: K
authors.lastname: Suzuki
authors.forename: David
authors.initials: D
authors.lastname: Walker
authors.forename: Osamu
authors.initials: O
authors.lastname: Takikawa
authors.forename: Rosanne
authors.initials: R
authors.lastname: Taylor
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Brew
mesh_terms: D000328:Adult; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics / Q000378:metabolism*; D016899:Interferon-beta / Q000502:physiology; D007371:Interferon-gamma / Q000494:pharmacology*; D007737:Kynurenine / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000502:physiology; D053858:Metabolic Networks and Pathways / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D012313:RNA / Q000235:genetics / Q000378:metabolism
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007737:Kynurenine; D012313:RNA; D016899:Interferon-beta; D007371:Interferon-gamma