Quick Search:

uzh logo
Browse by:

Zurich Open Repository and Archive

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.

View at publisher
Accepted Version


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.


23 citations in Web of Science®
26 citations in Scopus®
Google Scholar™



153 downloads since deposited on 16 Nov 2009
38 downloads since 12 months

Detailed statistics

Additional indexing

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
Date:May 2010
Deposited On:16 Nov 2009 13:15
Last Modified:05 Apr 2016 13:33
Publisher:Mary Ann Liebert
Publisher DOI:10.1089/scd.2009.0385
PubMed ID:19886804

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page