Activated human hepatic stellate cells induce myeloid derived suppressor cells from peripheral blood monocytes in a CD44-dependent fashion

Höchst, Bastian; Schildberg, Frank A.; Sauerborn, Pia; Gäbel, Yvonne A.; Gevensleben, Heidrun; Goltz, Diane; Heukamp, Lukas C.; Türler, Andreas; Ballmaier, Matthias; Gieseke, Friederike; Müller, Ingo; Kalff, Jörg C.; Kurts, Christian; Knolle, Percy A.; Diehl, Linda

doi:10.1016/j.jhep.2013.04.033

Cited by 125 publications

(108 citation statements)

References 44 publications

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“…Our findings provide another role for local changes in ROS such as H 2 O 2 in determining the outcome of tissue inflammation (42). In contrast to the study by Höchst et al (15), MDSC induced by purified catalase did not express arginase, but high levels of IDO, which indicates that HSC may provide additional signaling shaping the properties of MDSC induced from monocytes. Moreover, an IDO blocker 1-MT reduced the suppressive effect on T cell proliferation at a MDSC per T cell ratio of 1:2 and 1:4 suggesting that IDO may be partly responsible for the suppressive action of MDSC induced by catalase.…”

Section: Discussioncontrasting

confidence: 72%

“…1A, 1B). This cell population had a similar phenotype to MDSC induced by cocultures of monocytes with LX-2 or HSC as demonstrated by Höchst et al (15). We therefore cocultured monocytes with LX-2 cells and observed a similar induction of a CD14 + HLA-DR low/2 phenotype that reached similar levels to that observed with catalase coculture at day 5 (Fig.…”

Section: Purified Catalase Induced Functional Mdsc From Peripheral Blsupporting

confidence: 78%

“…HSC have been recently demonstrated to induce monocytic MDSC from mature peripheral blood monocytes in a cell-cell-contact-dependent manner (15). We speculated that this might be due to a microenvironmental change of metabolites that accumulate during the monocytic oxidative burst.…”

Section: Purified Catalase Induced Functional Mdsc From Peripheral Blmentioning

confidence: 93%

“…In murine transplantation models, whole allogenic livers, containing a stromal cell population, engraft well, whereas hepatocytes were rejected (7,12). However, in contrast to murine HSC (13) (14), MO-MDSC induction by human HSC (15) is dependent on cell-cell contact through CD44, a glycoprotein important for monocytic chemotaxis (16), suggestive of a previously unknown mechanism of MO-MDSC induction. In this study, we show that depletion of hydrogen peroxide (H 2 O 2 ) by soluble or stromally expressed catalase drives the induction of MO-MDSC from human monocytes.…”

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confidence: 99%

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Contact-Dependent Depletion of Hydrogen Peroxide by Catalase Is a Novel Mechanism of Myeloid-Derived Suppressor Cell Induction Operating in Human Hepatic Stellate Cells

Resheq

Ward

et al. 2015

The Journal of Immunology

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Myeloid-derived suppressor cells (MDSC) represent a unique cell population with distinct immunosuppressive properties that have been demonstrated to shape the outcome of malignant diseases. Recently, human hepatic stellate cells (HSC) have been reported to induce monocytic-MDSC from mature CD14+ monocytes in a contact-dependent manner. We now report a novel and unexpected mechanism by which CD14+HLADRlow/− suppressive cells are induced by catalase-mediated depletion of hydrogen peroxide (H2O2). Incubation of CD14+ monocytes with catalase led to a significant induction of functional MDSC compared with media alone, and H2O2 levels inversely correlated with MDSC frequency (r = −0.6555, p < 0.05). Catalase was detected in primary HSC and a stromal cell line, and addition of the competitive catalase inhibitor hydroxylamine resulted in a dose-dependent impairment of MDSC induction and concomitant increase of H2O2 levels. The NADPH-oxidase subunit gp91 was significantly increased in catalase-induced MDSC as determined by quantitative PCR outlining the importance of oxidative burst for the induction of MDSC. These findings represent a so far unrecognized link between immunosuppression by MDSC and metabolism. Moreover, this mechanism potentially explains how stromal cells can induce a favorable immunological microenvironment in the context of tissue oxidative stress such as occurs during cancer therapy.

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Section: Discussioncontrasting

confidence: 72%

Section: Purified Catalase Induced Functional Mdsc From Peripheral Blsupporting

confidence: 78%

Section: Purified Catalase Induced Functional Mdsc From Peripheral Blmentioning

confidence: 93%

mentioning

confidence: 99%

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Contact-Dependent Depletion of Hydrogen Peroxide by Catalase Is a Novel Mechanism of Myeloid-Derived Suppressor Cell Induction Operating in Human Hepatic Stellate Cells

Resheq

Ward

et al. 2015

The Journal of Immunology

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“…Maternal CD14 1 myelomonocytic cells have gained increasing attention, as these cells play a multifaceted role during early pregnancy; however, the definition of new subsets and the contribution of each population to the immunological microenvironment of pregnancy are just beginning to emerge. CD14 1 HLA-DR 2/low cells, a subset of CD14 1 myelomonocytic cells, exhibit potent suppressive activity 6 , and these cells are monocytic myeloid-derived suppressor cells (MOMDSCs) 7,8 , which have emerged as key immune modulators orchestrating lymphocyte responses. There is increasing interest in the role of MDSCs as tolerance-inducing cells during pregnancy 9,10 .…”

Section: Introductionmentioning

confidence: 99%

Human trophoblast cells induced MDSCs from peripheral blood CD14+ myelomonocytic cells via elevated levels of CCL2

Zhang

Sun

et al. 2015

Cell Mol Immunol

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Successful human pregnancy requires the maternal immune system to recognize and tolerate the semi-allogeneic fetus. Myeloid-derived suppressor cells (MDSCs), which are capable of inhibiting T-cell responses, are highly increased in the early stages of pregnancy. Although recent reports indicate a role for MDSCs in fetal-maternal tolerance, little is known about the expansion of MDSCs during pregnancy. In the present study, we demonstrated that the trophoblast cell line HTR8/SVneo could instruct peripheral CD14 1 myelomonocytic cells toward a novel subpopulation of MDSCs, denoted as CD14 1 HLA-DR 2/low cells, with suppressive activity and increased expression of IDO1, ARG-1, and COX2. After interaction with HTR8/SVneo cells, CD14 1 myelomonocytic cells secrete high levels of CCL2, promoting the expression of signal transducer and activator of transcription 3. We utilized a neutralizing monoclonal antibody to reveal the prominent role of CCL2 in the induction of CD14 1 HLA-DR 2/low MDSCs. In combination, the results of the present study support a novel role for the cross-talk between the trophoblast cell line HTR8/SVneo and maternal CD14 1 myelomonocytic cells in initiating MDSCs induction, prompting a tolerogenic immune response to ensure a successful pregnancy. Cellular & Molecular Immunology

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Remodeling Collagen Microenvironment in Liver Using a Biomimetic Nano‐Regulator for Reversal of Liver Fibrosis

Liang

Wang

et al. 2023

Advanced Science

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Liver fibrosis is a progressive histological manifestation that happens in almost all chronic liver diseases. An unabated liver fibrosis may eventually develop into liver cirrhosis or hepatocellular carcinoma. Yet, the strategy for reversal of liver fibrosis is still limited. Herein, a biomimetic nano-regulator (P-ZIF8-cirDNAzyme) is developed to affect both collagen synthesis and degradation in liver to remodel collagen microenvironment. It is found that Zn (II) interference can efficiently inhibit collagen synthesis in activated hepatic stellate cells (aHSC) by inactivating proline 4 hydroxylase and affecting many fibrosis-related signaling pathways. Meanwhile, Zn (II)-dependent circular DNAzymes (cirDNAzymes) are used to efficiently silence tissue inhibitors of metalloproteinase-1, accelerating the degradation of collagen. They act in concert to recover the balance between collagen deposition and degradation. Additionally, ZIF-8-cirDNAzyme is coated by platelet membrane (PM) for precisely targeting aHSC via PM's inflammatory tropism and CD62p-CD44 interaction. In carbon tetrachloride-induced fibrotic mice, P-ZIF-8-cirDNAzyme shows a potent anti-fibrotic effect, greatly reducing the expression of collagen by 73.12% and restoring liver function nearly to normal. This work proposes a prospective platform enabling ion interference and gene silencing, collectively acting in aHSC for reversal of liver fibrosis.

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Activated human hepatic stellate cells induce myeloid derived suppressor cells from peripheral blood monocytes in a CD44-dependent fashion

Cited by 125 publications

References 44 publications

Contact-Dependent Depletion of Hydrogen Peroxide by Catalase Is a Novel Mechanism of Myeloid-Derived Suppressor Cell Induction Operating in Human Hepatic Stellate Cells

Contact-Dependent Depletion of Hydrogen Peroxide by Catalase Is a Novel Mechanism of Myeloid-Derived Suppressor Cell Induction Operating in Human Hepatic Stellate Cells

Human trophoblast cells induced MDSCs from peripheral blood CD14+ myelomonocytic cells via elevated levels of CCL2

Remodeling Collagen Microenvironment in Liver Using a Biomimetic Nano‐Regulator for Reversal of Liver Fibrosis

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