Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-24070
Lanz, T; Opitz, C; Ho, P; Agrawal, A; Lutz, C; Weller, M; Mellor, A; Steinman, L; Wick, W; Platten, M (2010). Mouse mesenchymal stem cells suppress antigen-specific TH-cell immunity independent of indoleamine 2,3-dioxygenase 1 (IDO1). Stem Cells and Development, 19(5):657-668.
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Due to their immunosuppressive properties human mesenchymal stem cells (hMSC) represent a promising tool for cell-based therapies of autoimmune diseases such as multiple sclerosis (MS). Mouse MSC (mMSC) have been used extensively to characterize and optimize route of administration, motility, cellular targets and immunosuppressive mechanisms in mouse models of autoimmune diseases, such as experimental autoimmune encephalomyelitis (EAE). Tryptophan (trp) catabolism by indolamine-2,3-dioxygenase 1 (IDO1) is a chief endogenous metabolic pathway that tightly regulates unwanted immune responses through depletion of trp and generation of immunosuppressive kynurenines (kyn). IDO1 activity contributes to the immunosuppressive phenotype of hMSC. Here we demonstrate that although IDO1 is inducible in bone marrow-derived mMSC by proinflammatory stimuli such as interferon-gamma (IFN-gamma) and ligands of toll-like receptors (TLR), it does not lead to catabolism of trp in vitro. This failure to catabolize trp is not due to defective TLR signaling as demonstrated by induction of interleukin 6 (IL-6) by TLR activation. While mMSC suppressed the activation of antigen-specific myelin-oligodendrocyte glycoprotein (MOG)-reactive T cell receptor (TCR) transgenic T helper (TH) cells in coculture, neither pharmacologic inhibition nor genetic ablation of IDO1 reversed this suppressive effect. Finally, systemic administration of both, IDO1-proficient and phenotypically identical IDO1-deficient mMSC equally resulted in amelioration of EAE. mMSC, unlike hMSC, do not display IDO1-mediated suppression of antigen-specific T cell responses.
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|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurology|
|Dewey Decimal Classification:||610 Medicine & health|
|Deposited On:||16 Nov 2009 13:15|
|Last Modified:||27 Nov 2013 19:15|
|Publisher:||Mary Ann Liebert|
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