Human multipotent mesenchymal stromal cells inhibit proliferation of PBMCs independently of IFNgammaR1 signaling and IDO expression
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Human multipotent mesenchymal stromal cells inhibit proliferation of PBMCs independently of IFNgammaR1 signaling and IDO expression. / Gieseke, Friederike; Schütt, Burkhardt; Viebahn, Susanne; Koscielniak, Ewa; Friedrich, Wilhelm; Handgretinger, Rupert; Müller, Ingo.
In: BLOOD, Vol. 110, No. 6, 15.09.2007, p. 2197-200.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Human multipotent mesenchymal stromal cells inhibit proliferation of PBMCs independently of IFNgammaR1 signaling and IDO expression
AU - Gieseke, Friederike
AU - Schütt, Burkhardt
AU - Viebahn, Susanne
AU - Koscielniak, Ewa
AU - Friedrich, Wilhelm
AU - Handgretinger, Rupert
AU - Müller, Ingo
PY - 2007/9/15
Y1 - 2007/9/15
N2 - Multipotent mesenchymal stromal cells (MSCs) inhibit proliferation, helper, and effector functions in most if not all peripheral blood mononuclear cell (PBMC) subpopulations in vitro. The molecular mechanism is widely thought to imply tryptophan degradation by the interferon-gamma (IFNgamma)-induced expression of indoleamine 2,3-dioxygenase (IDO). However, IDO inhibitors were not able to restore proliferation of PBMCs in each case. Moreover, human MSCs with an IFNgamma receptor 1 (R1) defect inhibited proliferation of HLA-mismatched PBMCs to a similar extent as control MSCs. In contrast to healthy MSCs, IFNgammaR1-deficient MSCs showed no detectable mRNA for IDO-neither in the absence nor in the presence of recombinant human IFNgamma, nor in coculture with HLA-mismatched PBMCs. Based on gene expression profiling, we were able to show that insulin-like growth factor (IGF)-binding proteins contribute to the inhibitory mechanism of MSCs. Taken together, human MSCs exert important immunomodulatory functions in the absence of IFNgammaR1 signaling and IDO, partially accounted for by IGF-binding proteins.
AB - Multipotent mesenchymal stromal cells (MSCs) inhibit proliferation, helper, and effector functions in most if not all peripheral blood mononuclear cell (PBMC) subpopulations in vitro. The molecular mechanism is widely thought to imply tryptophan degradation by the interferon-gamma (IFNgamma)-induced expression of indoleamine 2,3-dioxygenase (IDO). However, IDO inhibitors were not able to restore proliferation of PBMCs in each case. Moreover, human MSCs with an IFNgamma receptor 1 (R1) defect inhibited proliferation of HLA-mismatched PBMCs to a similar extent as control MSCs. In contrast to healthy MSCs, IFNgammaR1-deficient MSCs showed no detectable mRNA for IDO-neither in the absence nor in the presence of recombinant human IFNgamma, nor in coculture with HLA-mismatched PBMCs. Based on gene expression profiling, we were able to show that insulin-like growth factor (IGF)-binding proteins contribute to the inhibitory mechanism of MSCs. Taken together, human MSCs exert important immunomodulatory functions in the absence of IFNgammaR1 signaling and IDO, partially accounted for by IGF-binding proteins.
KW - Cell Proliferation
KW - Cells, Cultured
KW - Child
KW - Chromatography, Affinity
KW - Humans
KW - Indoleamine-Pyrrole 2,3,-Dioxygenase
KW - Insulin-Like Growth Factor Binding Proteins
KW - Interferon-gamma
KW - Leukocytes, Mononuclear
KW - Mesenchymal Stromal Cells
KW - Multipotent Stem Cells
KW - Receptors, Interferon
KW - Signal Transduction
KW - Stromal Cells
U2 - 10.1182/blood-2007-04-083162
DO - 10.1182/blood-2007-04-083162
M3 - SCORING: Journal article
C2 - 17522338
VL - 110
SP - 2197
EP - 2200
JO - BLOOD
JF - BLOOD
SN - 0006-4971
IS - 6
ER -
