Interleukin-17C in Human Helicobacter pylori Gastritis

Tanaka, Shingo; Nagashima, Hiroyuki; Cruz, Modesto; Uchida, Tomohisa; Uotani, Takahiro; Abreu, José A. Jiménez; Mahachai, Varocha; Vilaichone, Ratha-Korn; Ratanachu‐ek, Thawee; Tshering, Lotay; Graham, David Y.; Yamaoka, Yoshio

doi:10.1128/iai.00389-17

Cited by 23 publications

(14 citation statements)

References 58 publications

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“…IL‐17RE‐deficient mice show decreased production of AMPs after C. rodentium infection, which results in increased bacterial burdens and decreased survival rates , clearly demonstrating the protective role of the IL‐17C–IL‐17RA/IL‐17RE axis against these infections. C. albicans , S. aureus , H. pylori , P. aeruginosa and herpes simplex virus also induce IL‐17C production by epithelial cells. Interestingly, P. aeruginosa‐ induced IL‐17C expression by lung epithelial cells in mice with pulmonary infections depends on the presence of IL‐17A , suggesting the existence of a network of IL‐17 family cytokines that regulate expression of each of its members.…”

Section: Role Of Non‐hematopoietic Cell‐derived Il‐17 Family Cytokinementioning

confidence: 99%

Interleukin‐17 family cytokines in protective immunity against infections: role of hematopoietic cell‐derived and non‐hematopoietic cell‐derived interleukin‐17s

Matsuzaki

Umemura

2018

Microbiology and Immunology

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Interleukin-17 family cytokines, consisting of six members, participate in immune response in infections and autoimmune and inflammatory diseases. The prototype cytokine of the family, IL-17A, was originally identified from CD4þ T cells which are now termed Th17 cells. Later, IL-17A-producing cells were expanded to include various hematopoietic cells, namely CD8þ T cells (Tc17), invariant NKT cells, gd T cells, non-T non-B lymphocytes (termed type 3 innate lymphoid cells) and neutrophils. Some IL-17 family cytokines other than IL-17A are also expressed by CD4þ T cells: IL-17E by Th2 cells and IL-17F by Th17 cells. IL-17A and IL-17F induce expression of pro-inflammatory cytokines to induce inflammation and anti-microbial peptides to kill pathogens, whereas IL-17E induces allergic inflammation. However, the functions of other IL-17 family cytokines have been unclear. Recent studies have shown that IL-17B and IL-17C are expressed by epithelial rather than hematopoietic cells. Interestingly, expression of IL-17E and IL-17F by epithelial cells has also been reported and epithelial cell-derived IL-17 family cytokines shown to play important roles in immune responses to infections at epithelial sites. In this review, we summarize current information on hematopoietic cell-derived IL-17A and non-hematopoietic cell-derived IL-17B, IL-17C, IL-17D, IL-17E and IL-17F in infections and propose functional differences between these two categories of IL-17 family cytokines.

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Section: Role Of Non‐hematopoietic Cell‐derived Il‐17 Family Cytokinementioning

confidence: 99%

Interleukin‐17 family cytokines in protective immunity against infections: role of hematopoietic cell‐derived and non‐hematopoietic cell‐derived interleukin‐17s

Matsuzaki

Umemura

2018

Microbiology and Immunology

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“…In human gastric mucosa, Helicobacter pylori infection was associated with a significant increase in IL-17C expression in gastric mucosa, and its role is still undetermined. 46 Our study suggests that the ability to alter the expression of IL-17 may represent a mechanism underlying the anti-infection and protective role of TSLP in the cornea, and IL-17C, known to be expressed mostly by epithelia, may play a role in TSLP-TSLPR-mediated innate protection in the cornea.…”

Section: Discussionmentioning

confidence: 73%

TSLP Protects Corneas FromPseudomonas aeruginosaInfection by Regulating Dendritic Cells and IL-23-IL-17 Pathway

Cui

Gao

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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PurposeWe sought to determine the role of epithelium-produced thymic stromal lymphopoietin (TSLP) and its underlying mechanisms in corneal innate immune defense against Pseudomonas (P.) aeruginosa keratitis.MethodsThe expression of TSLP and TSLPR in cultured human corneal epithelial cells (HCECs) and mouse corneas was determined by PCR, Western, and/or ELISA. Cellular localization of TSLP receptor (TSLPR) was determined by whole mount confocal microscopy. TSLP-TSLPR signaling was downregulated by neutralizing antibodies and/or small interfering (si)RNA; their effects on the severity of P. aeruginosa–keratitis and cytokine expression were assessed using clinical scoring, bacterial counting, PMN infiltration, and real-time PCR. The role of dendritic cells (DCs) in corneal innate immunity was determined by local DC depletion using CD11c-DTR mice.ResultsP. aeruginosa–infection induced the expression of TSLP and TSLPR in both cultured primary HCECs and in C57BL/6 mouse corneas. While TSLP was mostly expressed by epithelial cells, CD11c-positive cells were positive for TSLPR. Targeting TSLP or TSLPR with neutralizing antibodies or TSLPR with siRNA resulted in more severe keratitis, attributable to an increase in bacterial burden and PMN infiltration. TSLPR neutralization significantly suppressed infection-induced TSLP and interleukin (IL)-17C expression and augmented the expression of IL-23 and IL-17A. Local depletion of DCs markedly increased the severity of keratitis and exhibited no effects on TSLP and IL-23 expression while suppressing IL-17A and C expression in P. aeruginosa–infected corneas.ConclusionsThe epithelium-expressed TSLP plays a protective role in P. aeruginosa keratitis through targeting of DCs and in an IL-23/IL-17 signaling pathway-related manner.

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“…After sample size selection, data sets GSE5081, GSE27411, and GSE60427 were selected for this study (Table S1). GSE5081 was acquired on an Affymetrix Human Genome U133 Plus 2.0 Array (Affymetrix Inc., San Diego, CA), and included 32 gastric erosions and healthy adjacent mucosa samples that were classified as either HP + or HP − (Tanaka et al, 2017). GSE27411 was acquired on Illumina HumanRef‐8 v2.0 Expression BeadChips (Illumina Inc., San Diego, CA), and included 18 antrum and corpus mucosa samples that were HP + , HP − , or undetermined (Nookaew et al, 2013).…”

Section: Methodsmentioning

confidence: 99%

Bioinformatic identification of key pathways, hub genes, and microbiota for therapeutic intervention in Helicobacter pylori infection

Chen

et al. 2020

Journal Cellular Physiology

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The pathogenic mechanisms of Helicobacter pylori infection remain to be defined, and potential interventional microbiota are just beginning to be identified. In this study, gene-set enrichment analysis (GSEA) was used to integrate three H. pylori infection microarray data sets from the gene expression omnibus database and identified ten hallmark gene sets and 35 Kyoto encyclopedia of genes and genomes (KEGG) pathways that differed between healthy and Helicobacter pylori-infected individuals. Weighted gene co-expression network analysis (WGCNA) performed on two of the data sets identified three key gene coexpression modules. These modules contained 54 enriched KEGG pathways, 25 of which overlapped with the GSEA analysis, suggesting potentially important roles in H. pylori-infection. We selected 116 hub genes from the three key modules for in vitro validation at the transcriptional level using H. pylori Sydney Strain 1 and verified the upregulation of 80. WGCNA of the microbiomes based on 20 mucosal samples and a sequence read archive data set revealed four microbiota modules correlated with H. pylori infection. The negatively correlated modules contained 11 microbiome families. These findings provide new insight into the pathogenesis of H. pylori infection and systematically identify 25 key pathways, 80 upregulated hub genes, and 11 families of candidate interventional microbiota for further research.

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Interleukin-17C in Human Helicobacter pylori Gastritis

Cited by 23 publications

References 58 publications

Interleukin‐17 family cytokines in protective immunity against infections: role of hematopoietic cell‐derived and non‐hematopoietic cell‐derived interleukin‐17s

Interleukin‐17 family cytokines in protective immunity against infections: role of hematopoietic cell‐derived and non‐hematopoietic cell‐derived interleukin‐17s

TSLP Protects Corneas FromPseudomonas aeruginosaInfection by Regulating Dendritic Cells and IL-23-IL-17 Pathway

Bioinformatic identification of key pathways, hub genes, and microbiota for therapeutic intervention in Helicobacter pylori infection

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