Increased programmed death-ligand-1 expression in human gastric epithelial cells in<i>Helicobacter pylori</i>infection

Wu, Yan-Guang; Lin, Chung-Wu; Ks, Cheng; Lin, Cheng Wen; Ym, Wang; Lin, I-T; Chou, Y-H; Hsu, Ping-Ning

doi:10.1111/j.1365-2249.2010.04217.x

Cited by 76 publications

(78 citation statements)

References 32 publications

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“…2A). Studies showed that PD-L1 was detectable in human gastric epithelial cells (17) and colonic epithelial cells (13,15,18). We confirmed that PD-L1 mRNA and protein were constitutively expressed in freshly isolated small intestinal epithelial cells (IECs) from naïve WT mice ( Supplementary Fig.1).…”

Section: Sepsis Increases Pd-l1 Expression In the Mouse Intestinesupporting

confidence: 63%

“…Figure 4C Accumulating evidence has demonstrated that the PD-1/PD-L1 pathway plays an important role in regulating the immune-inflammatory response during sepsis, as sepsis can up-regulate PD-L1 expression on a variety of immune cells both in humans (2,14). In the gastrointestinal tract, human gastric epithelial cells express basal levels of PD-L1, and its expression is significantly increased when exposed to Helicobacter Pylori (17). Importantly, the current study is the first report to show that the expression of PD-L1 is markedly elevated in the colon of patients with sepsis.…”

Section: Junction Integritymentioning

confidence: 99%

“…Additionally, studies have indicated that PD-L1 is not only expressed, but also involved in intestinal mucosal inflammation and regulates gut immune tolerance (15,16). PD-L1 has been reported to be expressed on colonic and gastric epithelial cells, and in select situations, it contributes to the interaction between epithelial cells and lymphocytes (15,17,18). Intestinal epithelium is the key component of intestinal barrier, which separates bacteria and toxic substances in the gut from the sub-mucosal lymphoid tissue and maintaining intestinal immune homeostasis.…”

Section: Introductionmentioning

confidence: 99%

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A Novel Role for Programmed Cell Death Receptor Ligand-1 in Sepsis-Induced Intestinal Dysfunction

Chung

Chen

et al. 2016

Mol Med

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Studies imply that intestinal barrier dysfunction is a key contributor to morbid events associated with sepsis. Recently, co-inhibitory molecule, programmed death-ligand1 (PD-L1) has been shown to be involved in the regulation of intestinal immune tolerance and/or inflammation. Our previous studies showed that PD-L1 gene deficiency reduced sepsis-induced intestinal injury morphologically. However, it isn't known how PD-L1 expression impacts intestinal barrier dysfunction during sepsis. Here we tested the hypothesis that PD-L1 expressed on intestinal epithelial cells (IECs) has a role in sepsis-induced intestinal barrier dysfunction. To address this, C57BL/6 or PD-L1 gene knockout mice were subjected to experimental sepsis and PD-L1 expression, intestinal permeability, tissue cytokine levels were assessed. Subsequently, septic or non-septic patient colonic samples (assigned by pathology report) were immunohistochemically stained for PD-L1 I a blinded fashion. Finally, human Caco2 cells were used for in vitro studies.The results demonstrated that PD-L1 was constitutively expressed and sepsis significantly upregulates PD-L1 in IECs from C57BL/6 mice. Concurrently, we observed an increased PD-L1 expression in colon tissue samples from septic patients. PD-L1 gene deficiency reduced ileal permeability, tissue levels of IL-6, TNF-α and MCP-1, and prevented ileal tight junction protein loss compared to WT after sepsis. Comparatively, while Caco2 cell monolayers responded to inflammatory cytokine stimulation also with elevated PD-L1 expression, increased monolayer permeability and altering/decreasing monolayer tight junction protein morphology/expression; these changes were reversed by PD-L1 blocking antibody. Together these data indicate that ligation of ICE PD-L1 plays a novel role in mediating the pathophysiology of sepsis-induced intestinal barrier dysfunction.

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Section: Sepsis Increases Pd-l1 Expression In the Mouse Intestinesupporting

confidence: 63%

Section: Junction Integritymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A Novel Role for Programmed Cell Death Receptor Ligand-1 in Sepsis-Induced Intestinal Dysfunction

Chung

Chen

et al. 2016

Mol Med

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“…Programmed death 1 (PD-1), a negative regulator for activation, expansion and acquisition of effector functions of T cells, is well involved in pathogen evasion strategies [33,34]. Although extensive studies have been performed on function of PD-1, as so far regulation mechanism of PD-1 expression has not been reported.…”

Section: Pathogen Evasionmentioning

confidence: 99%

Some research advances of immune mechanism during infection in China

Yang

2011

Sci. China Life Sci.

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“…Flow cytometry analysis was performed using a technique described previously (14). The CD4 ϩ T cells were gated from the forward scatter (FSC) low versus CD4 ϩ T cells, which correspond to the lymphocyte population according to our previous data (15).…”

mentioning

confidence: 99%

Expression of CD25^highRegulatory T Cells and PD-1 in Gastric Infiltrating CD4⁺T Lymphocytes in Patients with Helicobacter pylori Infection

Chen

Kao³

et al. 2011

Clin. Vaccine Immunol.

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We observed by flow cytometry that the frequency of both gastric infiltrating Tregs and PD-1-positive CD4 T cells is correlated with the density of Helicobacter pylori, suggesting that cellular immunity against this pathogen is inhibited.Helicobacter pylori, a common human pathogen, infects about 50% of the world's population (9, 10). Many studies have confirmed that the pathogenesis of H. pylori infection is probably due largely to the host immune system, particularly the cellular immune response. However, the mechanism by which H. pylori negatively regulates the immune response against the bacteria is not completely understood.In recent years, regulatory T cells (Tregs) and related negative regulatory molecules have been a focus of research on the immune mechanisms of diseases. Evidence indicates that removal or reduction of Tregs can enhance immune responses against infectious microbes (1,2,5,6,8,(11)(12)(13)16). Expression of programmed cell death 1 (PD-1, also called CD279), a negative regulatory molecule in the CD28/B7 family, is induced on CD4 ϩ T cells, CD8 ϩ T cells, natural killer T cells, B cells, and activated monocytes during the course of many diseases. B and T lymphocyte attenuator (BTLA), a newly discovered member of the CD28 family of costimulatory molecules, may have inhibitory function similar to that of PD-1.The PD-1 signaling pathway is involved in chronic bacterial infection and may be a potential therapeutic target. However, the role of BTLA in H. pylori infection has not been investigated. In this study, we analyzed the frequency of gastric infiltrating CD4 ϩ CD25 high Tregs in patients with H. pylori infection, as well as the expression of PD-1 and BTLA on gastric infiltrating CD4 ϩ T cells, and their relationships with H. pylorirelated clinical markers.Biopsy specimens of the gastric antrum were obtained from patients undergoing gastric endoscopy for dyspepsia at China Medical University Hospital. There were 38 H. pylori-infected subjects enrolled in this study. Peripheral blood samples from the same patients served as the control. The presence of H. pylori infection was determined by histopathologic examination (including Giemsa staining) and/or by a positive result for a rapid urease test performed on at least one additional biopsy sample. The density of H. pylori was analyzed as suggested by the updated Sydney system (4): 0, absent; 1, mild; 2, moderate; and 3, marked. The degree of inflammation present in the histological specimens was also classified according to the updated Sydney system. Biopsy specimens of the gastric antrum were collected into sterile collection medium (calcium-and magnesium-free Hanks' balanced salt solution [HBSS] with 5% fetal calf serum and penicillin plus streptomycin). The collected tissues were immediately placed in ice-cold RPMI 1640 complete medium (Gibco BRL, Gaithersburg, MD) which contained 10% fetal calf serum supplemented with penicillin (50 IU/ml), streptomycin (50 g/ml), L-glutamine (2 mM), and sodium pyruvate (1 mM). Gastric infiltrating lymph...

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Increased programmed death-ligand-1 expression in human gastric epithelial cells inHelicobacter pyloriinfection

Abstract: Summary B7-H1 [programmed death-ligand-1 (PD-L1

Cited by 76 publications

References 32 publications

A Novel Role for Programmed Cell Death Receptor Ligand-1 in Sepsis-Induced Intestinal Dysfunction

A Novel Role for Programmed Cell Death Receptor Ligand-1 in Sepsis-Induced Intestinal Dysfunction

Some research advances of immune mechanism during infection in China

Expression of CD25^highRegulatory T Cells and PD-1 in Gastric Infiltrating CD4⁺T Lymphocytes in Patients with Helicobacter pylori Infection

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Increased programmed death-ligand-1 expression in human gastric epithelial cells inHelicobacter pyloriinfection

Abstract: Summary B7-H1 [programmed death-ligand-1 (PD-L1

Cited by 76 publications

References 32 publications

A Novel Role for Programmed Cell Death Receptor Ligand-1 in Sepsis-Induced Intestinal Dysfunction

A Novel Role for Programmed Cell Death Receptor Ligand-1 in Sepsis-Induced Intestinal Dysfunction

Some research advances of immune mechanism during infection in China

Expression of CD25highRegulatory T Cells and PD-1 in Gastric Infiltrating CD4+T Lymphocytes in Patients with Helicobacter pylori Infection

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Expression of CD25^highRegulatory T Cells and PD-1 in Gastric Infiltrating CD4⁺T Lymphocytes in Patients with Helicobacter pylori Infection