Journal Article

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

Lamoury, Francois M. J., Suzuki, Kazuo, Brew, Bruce J., Takikawa, Osamu, Walker, David, Taylor, Rosanne, Croitoru-Lamoury, Juliana, Caristo, Michael

2011

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Activation / Adult / Animals / Antimicrobial activity / Biocompatibility / Biomedical materials / Bone marrow / Brain research / Cell Biology/Gene Expression / Cell Differentiation - drug effects / Cell Differentiation - genetics / Cell division / Cell growth / Cell proliferation / Cell Proliferation - drug effects / Cells, Cultured / Developmental Biology/Cell Differentiation / Developmental Biology/Stem Cells / Differentiation / Dioxygenase / Enzyme Activation - drug effects / Enzymes / Gene Expression Regulation, Enzymologic - drug effects / Hematology / Hospitals / Humans / Immune response / Indoleamine-Pyrrole 2,3,-Dioxygenase - genetics / Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism / Infections / Interferon / Interferon-beta - physiology / Interferon-gamma - pharmacology / Kynurenine - metabolism / Male / Medical research / Mesenchymal stem cells / Mesenchymal Stromal Cells - drug effects / Mesenchymal Stromal Cells - enzymology / Mesenchymal Stromal Cells - metabolism / Mesenchymal Stromal Cells - physiology / Mesenchyme / Metabolic Networks and Pathways - drug effects / Metabolic Networks and Pathways - genetics / Metabolism / Metabolites / Mice / Mice, Inbred C57BL / Modulation / Multiple sclerosis / Neural stem cells / Neurogenesis / Neurological Disorders/Multiple Sclerosis and Related Disorders / Neuroscience/Neurobiology of Disease and Regeneration / Physiology / RNA - genetics / RNA - metabolism / Senescence / Stem cell transplantation / Stem cells / Transcription / Tryptophan / γ-Interferon