Activated T-cells and pro-inflammatory cytokines differentially regulate prostaglandin E2 secretion by mesenchymal stem cells

Hegyi, Beáta; Kudlik, Gyöngyi; Monostori, Éva; Uher, Ferenc

doi:10.1016/j.bbrc.2012.01.150

Cited by 67 publications

(50 citation statements)

References 30 publications

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“…The requirements included purity, and mature but inactive state. MSCs used in these experiments met the criteria for murine MSCs according to morphology, flow cytometry analysis of cells surface markers and differentiation potential (as we described earlier [24]). Treatment of bone marrow nucleated cells with M-CSF for one week resulted in a homogenous population of mature (CD11b + F4/80 + ) and naïve (Ly-6c -MHC-II -) MΦs (BM-Ms) (Fig.…”

Section: Characterization and Comparison Of Mφs Isolated From Bone Mamentioning

confidence: 99%

Mesenchymal stem cells promote macrophage polarization toward M2b-like cells

Kudlik

Hegyi

Czibula

et al. 2016

Experimental Cell Research

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Section: Characterization and Comparison Of Mφs Isolated From Bone Mamentioning

confidence: 99%

Mesenchymal stem cells promote macrophage polarization toward M2b-like cells

Kudlik

Hegyi

Czibula

et al. 2016

Experimental Cell Research

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“…In human MSC, the reported pathways of immune suppression by MSC include the indoleamine 2,3-deoxygenase (IDO) [21,22], cyclooxygenase [23][24][25], TGF-b [26], soluble IL-1Ra [27,28], soluble MHC [29,30], and the PD-L1 pathways [31,32]. In general however, the IDO-dependent pathway is considered the primary mechanism of human MSC suppression of activated immune effector cells [21].…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of Immune Suppression Utilized by Canine Adipose and Bone Marrow-Derived Mesenchymal Stem Cells

ChowLyndah

JohnsonValerie

CoyJonathan

et al. 2017

Stem Cells and Development

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Mesenchymal stem cells (MSCs) from rodents and humans have been shown to suppress T cells by distinct primary pathways, with nitric oxide (NO)-dependent pathways dominating in rodents and indoleamine 2,3-deoxygenase (IDO)-dependent pathways dominating in humans. However, the immune suppressive pathways utilized by canine MSC have not been thoroughly studied, nor have bone marrow-derived MSC (BM-MSC) and adipose-derived MSC (Ad-MSC) been directly compared for their immune modulatory potency or pathway utilization. Therefore, canine BM-MSC and Ad-MSC were generated in vitro and their potency in suppressing T cell proliferation and cytokine production was compared, and differential gene expression. Mechanisms of T cells suppression were also investigated for both MSC types. We found that BM-MSC and Ad-MSC were roughly equivalent in terms of their ability to suppress T cell activation. However, the two MSC types used both shared and distinct biochemical pathways to suppress T cell activation. Ad-MSC utilized TGF-b signaling pathways and adenosine signaling to suppress T cell activation, whereas BM-MSC used cyclooxygenase, TGF-b and adenosine signaling pathways to suppress T cell activation. These results indicate that canine MSC are distinct from human and rodent MSC terms of their immune suppressive pathways, relying primarily on cyclooxygenase and TGF-b pathways for T cell suppression, rather than on NO or IDO-mediated pathways.

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“…ASC activation or suppression of one or more specific Tcell subsets may significantly affect the observed overall growth inhibition or stimulation of T cells [5][6][7]9,[12][13][14][15][16][17]. Several studies have demonstrated that ASCs inhibit cells of both the innate and adaptive immune response through secretion of soluble factors such as prostaglandin E 2 , TGF-b1, hepatocyte growth factor, and production of factors that include inducible nitric oxide synthase and indoleamine 2,3-dioxygenase [7,9,12,13,[20][21][22].…”

Section: Cd4mentioning

confidence: 99%

Human Adipose-Derived Stromal/Stem Cells Induce Functional CD4⁺CD25⁺FoxP3⁺CD127⁻Regulatory T Cells Under Low Oxygen Culture Conditions

Frazier

McLachlan

Gimble

et al. 2014

Stem Cells and Development

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Human adipose tissue stromal/stem cells (ASCs) are known to induce proliferation of resting T cells under ambient (21%) O 2 conditions; however, ASCs exist physiologically under lower oxygen (5% O 2 ) conditions in adipose tissue. The effects of low oxygen levels on ASC immunomodulation of T cells are unknown. In this study, we show that ASCs stimulated proliferation of naive CD4+ T cells and the percentage of CD25 + T cells was significantly increased under both low and ambient O 2 . Forkhead box P3 (FoxP3) and transforming growth factor beta (TGF-b) mRNA expression were significantly increased when ASCs were cocultured with CD4 + T cells under low compared with ambient O 2 conditions. The low O 2 -induced regulatory T cells (iT regs ) exhibited functionality when added to mixed lymphocyte reactions as demonstrated by inhibition of peripheral blood mononuclear cell proliferation, and by > 300-fold increase in FoxP3 mRNA, and > 2-fold increase in TGF-b mRNA expression. These results demonstrate that under physiologically relevant low O 2 conditions, direct contact of human ASCs with naive CD4 + T cells induced functional iT regs .

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Activated T-cells and pro-inflammatory cytokines differentially regulate prostaglandin E2 secretion by mesenchymal stem cells

Cited by 67 publications

References 30 publications

Mesenchymal stem cells promote macrophage polarization toward M2b-like cells

Mesenchymal stem cells promote macrophage polarization toward M2b-like cells

Mechanisms of Immune Suppression Utilized by Canine Adipose and Bone Marrow-Derived Mesenchymal Stem Cells

Human Adipose-Derived Stromal/Stem Cells Induce Functional CD4⁺CD25⁺FoxP3⁺CD127⁻Regulatory T Cells Under Low Oxygen Culture Conditions

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Activated T-cells and pro-inflammatory cytokines differentially regulate prostaglandin E2 secretion by mesenchymal stem cells

Cited by 67 publications

References 30 publications

Mesenchymal stem cells promote macrophage polarization toward M2b-like cells

Mesenchymal stem cells promote macrophage polarization toward M2b-like cells

Mechanisms of Immune Suppression Utilized by Canine Adipose and Bone Marrow-Derived Mesenchymal Stem Cells

Human Adipose-Derived Stromal/Stem Cells Induce Functional CD4+CD25+FoxP3+CD127−Regulatory T Cells Under Low Oxygen Culture Conditions

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Human Adipose-Derived Stromal/Stem Cells Induce Functional CD4⁺CD25⁺FoxP3⁺CD127⁻Regulatory T Cells Under Low Oxygen Culture Conditions