Mouse mesenchymal stem cells suppress antigen-specific TH cell immunity independent of indoleamine 2,3-dioxygenase 1 (IDO1)

Tobias V. Lanz, Christiane A. Opitz, Peggy P. Ho, Ankur Agrawal, Christian Lutz, Michael Weller, Andrew L. Mellor, Lawrence Steinman, Wolfgang Wick, Michael Platten

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

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-g (IFN-g) 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 co-culture, 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.

Original languageEnglish (US)
Pages (from-to)657-668
Number of pages12
JournalStem Cells and Development
Volume19
Issue number5
DOIs
StatePublished - May 1 2010

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Indoleamine-Pyrrole 2,3,-Dioxygenase
Helper-Inducer T-Lymphocytes
Mesenchymal Stromal Cells
Immunity
Immunosuppressive Agents
Antigens
Tryptophan
Toll-Like Receptors
Autoimmune Experimental Encephalomyelitis
Autoimmune Diseases
Myelin-Oligodendrocyte Glycoprotein
Kynurenine
Cell- and Tissue-Based Therapy
Coculture Techniques
T-Cell Antigen Receptor
Metabolic Networks and Pathways
Interferons
Multiple Sclerosis
Interleukin-6
Bone Marrow

ASJC Scopus subject areas

  • Hematology
  • Developmental Biology
  • Cell Biology

Cite this

Mouse mesenchymal stem cells suppress antigen-specific TH cell immunity independent of indoleamine 2,3-dioxygenase 1 (IDO1). / Lanz, Tobias V.; Opitz, Christiane A.; Ho, Peggy P.; Agrawal, Ankur; Lutz, Christian; Weller, Michael; Mellor, Andrew L.; Steinman, Lawrence; Wick, Wolfgang; Platten, Michael.

In: Stem Cells and Development, Vol. 19, No. 5, 01.05.2010, p. 657-668.

Research output: Contribution to journalArticle

Lanz, TV, Opitz, CA, Ho, PP, Agrawal, A, Lutz, C, Weller, M, Mellor, AL, 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, vol. 19, no. 5, pp. 657-668. https://doi.org/10.1089/scd.2009.0385
Lanz, Tobias V. ; Opitz, Christiane A. ; Ho, Peggy P. ; Agrawal, Ankur ; Lutz, Christian ; Weller, Michael ; Mellor, Andrew L. ; Steinman, Lawrence ; Wick, Wolfgang ; Platten, Michael. / Mouse mesenchymal stem cells suppress antigen-specific TH cell immunity independent of indoleamine 2,3-dioxygenase 1 (IDO1). In: Stem Cells and Development. 2010 ; Vol. 19, No. 5. pp. 657-668.
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