Liver Myofibroblasts Regulate Infiltration and Positioning of Lymphocytes in Human Liver

Holt, Andrew; Haughton, Emma Louise; Lalor, Patricia F.; Filer, Andrew; Buckley, Christopher D.; Adams, David H.

doi:10.1053/j.gastro.2008.10.020

Cited by 127 publications

(113 citation statements)

References 36 publications

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“…Conversely, MIG and IP-10 are secreted not only by endothelial cells but also by cholangiocytes and activated stellate cells [29,30]. If so, in PBC, IP-10 and MIG might be secreted by endothelial cells and direct T cells into the portal tracts.…”

Section: Discussionmentioning

confidence: 99%

CXCR3 axis in patients with primary biliary cirrhosis: a possible novel mechanism of the effect of ursodeoxycholic acid

Manousou

Kolios

Drygiannakis

et al. 2013

Clinical and Experimental Immunology

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Section: Discussionmentioning

confidence: 99%

CXCR3 axis in patients with primary biliary cirrhosis: a possible novel mechanism of the effect of ursodeoxycholic acid

Manousou

Kolios

Drygiannakis

et al. 2013

Clinical and Experimental Immunology

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“…The aLMF-conditioned media had chemotactic activity for lymphocytes, which was partially inhibited by pertussis toxin, implying a requirement for GPCR signaling. Additionally, contribution of GPCR-independent lymphocyte chemotaxis by IL-6, hepatocyte growth factor, and VEGF was also reported [151] .…”

Section: Livermentioning

confidence: 98%

“…However, these signaling events are not well elucidated despite well-documented observations of lymphocyte recruitment to tissues via endothelium. Holt et al [151] suggested that activated human liver myofibroblasts (aLMF) affect the migration and accumulation of lymphocytes within the inflamed liver. Also, when cultured in vitro, aLMF from inflamed human livers and hepatic stellate cells from non-inflamed livers secrete a distinct profile of cytokines and chemokines.…”

Section: Livermentioning

confidence: 99%

Chemokines, chemokine receptors and the gastrointestinal system

Miyazaki¹,

Takabe²,

Yeudall³

2013

WJG

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Core tip: The chemokine network makes an attractive target for therapeutic intervention in many tumor types, including those of the gastrointestinal tract. However, we need to define more selective and specific targets, to minimize systemic side effects during treatment. INTRODUCTION Cancer development and progression in the gastrointestinal tractCancer is a disease in which normal cells acquire genetic and epigenetic abnormalities [1,2] , leading to disorientation of conventional processes for the maintenance of normal cell physiology. These aberrant genetic and epigenetic modifications to the normal cell induce abnormal cell motility, proliferation, and survival, eventually enabling these cells to invade into adjacent tissues and even to migrate to regional or distant organs where they may grow continuously as metastatic lesions [3] . For many cancer patients, metastasis is generally the major cause of disease-related death [4,5] . Therefore, it is indispensable to elucidate the basic molecular mechanisms of tumor development to identify effective therapeutic targets, which can possibly reduce the side-effects of treatment, and define useful molecular markers for early detection and prediction of disease course. Especially, the newly emerged concept of personalized medicine may require in-depth assessment of potential therapeutic molecular target(s) in each individual case through analysis of sig- REVIEW Chemokines, chemokine receptors and the gastrointestinal system AbstractThe biological properties of tumor cells are known to be regulated by a multitude of cytokines and growth factors, which include epidermal growth factor receptor agonists and members of the transforming growth factor β family. Furthermore, the recent explosion of research in the field of chemokine function as mediators of tumor progression has led to the possibility that these small, immunomodulatory proteins also play key roles in carcinogenesis and may, therefore, be potential targets for novel therapeutic approaches. In this review, we will summarize recently reported findings in chemokine biology with a focus on the gastrointestinal tract.

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“…HSC were isolated and cultured as described previously (11). In brief, HSC were isolated from normal or resected human liver by pronase/collagenase digestion, followed by buoyancy centrifugation.…”

Section: Isolation Of Hscmentioning

confidence: 99%

“…However, in contrast to cells isolated from malignant melanomas, primary hepatocytes are not capable of inducing MO-MDSC from mature CD14 + monocytes, suggesting that accessory cells or factors are required for differentiation (7). Hepatic stellate cells (HSC) are liver resident stromal cells (8,9) that exhibit immunoregulatory functions such as the induction of regulatory T cells (10) or the control of lymphocytic chemotaxis by secretion of various chemokines such as CCL2 (11). In murine transplantation models, whole allogenic livers, containing a stromal cell population, engraft well, whereas hepatocytes were rejected (7,12).…”

mentioning

confidence: 99%

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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Liver Myofibroblasts Regulate Infiltration and Positioning of Lymphocytes in Human Liver

Cited by 127 publications

References 36 publications

CXCR3 axis in patients with primary biliary cirrhosis: a possible novel mechanism of the effect of ursodeoxycholic acid

CXCR3 axis in patients with primary biliary cirrhosis: a possible novel mechanism of the effect of ursodeoxycholic acid

Chemokines, chemokine receptors and the gastrointestinal system

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

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