CD103 Promotes the Pro-inflammatory Response of Gastric Resident CD4+ T Cell in Helicobacter pylori-Positive Gastritis

Chen, Peiyu; Ming, Siqi; Lao, Juanfeng; Li, Chunna; Wang, Hongli; Xiong, Lin; Zhang, Shunxian; Liang, Zhongxing; Niu, Xiaoli; Deng, Simei; Geng, Lanlan; Wu, Minhao; Wu, Yongjian; Gong, Sitang

doi:10.3389/fcimb.2020.00436

Cited by 10 publications

(8 citation statements)

References 61 publications

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“…All of the 51 patients were diagnosed as H. pylori -positive gastritis with pathological changes of mucosa, whereas 35 healthy controls are with H. pylori -negative results and normal mucosa (See Table 1 ). Gastritis was diagnosed when the depth of damaged mucosal tissue was <5 mm, while the depth of damaged tissue was >5 mm in gastric ulcer patients ( 21 ).…”

Section: Methodsmentioning

confidence: 99%

“…Gastritis induced by H. pylori infection is characterized by excessive mucosal inflammation, which is represented by the hypersecretion of mucus and cytokines, and inflammatory cell infiltration ( 20 , 21 ). Gastritis may lead to gastric perforation, gastrorrhagia, ulcers, and even worse, stomach cancer after further development ( 22 , 23 ).…”

Section: Introductionmentioning

confidence: 99%

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OX40L/OX40 Signal Promotes IL-9 Production by Mucosal MAIT Cells During Helicobacter pylori Infection

et al. 2021

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Mucosal associated invariant T (MAIT) cells play a critical role in Helicobacter pylori (H. pylori)-induced gastritis by promoting mucosal inflammation and aggravating mucosal injuries (1, 2). However, the underlying mechanism and key molecules involved are still uncertain. Here we identified OX40, a co-stimulatory molecule mainly expressed on T cells, as a critical regulator to promote proliferation and IL-9 production by MAIT cells and facilitate mucosal inflammation in H. pylori-positive gastritis patients. Serum examination revealed an increased level of IL-9 in gastritis patients. Meanwhile, OX40 expression was increased in mucosal MAIT cells, and its ligand OX40L was also up-regulated in mucosal dendritic cells (DCs) of gastritis patients, compared with healthy controls. Further results demonstrated that activation of the OX40/OX40L pathway promoted IL-9 production by MAIT cells, and MAIT cells displayed a highly-activated phenotype after the cross-linking of OX40 and OX40L. Moreover, the level of IL-9 produced by MAIT cells was positively correlated with inflammatory indexes in the gastric mucosa, suggesting the potential role of IL-9-producing MAIT cells in mucosal inflammation. Taken together, we elucidated that OX40/OX40L axis promoted mucosal MAIT cell proliferation and IL-9 production in H. pylori-induced gastritis, which may provide potential targeting strategies for gastritis treatment.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

OX40L/OX40 Signal Promotes IL-9 Production by Mucosal MAIT Cells During Helicobacter pylori Infection

et al. 2021

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“…The procedure of cell staining and flow cytometry was previously described ( 5 ). For intracellular staining of IL-21, gastric CD4 + T cells were restimulated with 1 μg/ml anti-CD3 Ab (Clone UCHT1, BD), 1 μg/ml anti-CD28 Ab (Clone CD28.2, BD), and 3 μg/ml brefeldinA (eBioscience, CA, USA) for 12 h. The intracellular fixation/permeabilization buffer set (eBioscience, CA, USA) was used in IL-21 staining.…”

Section: Methodsmentioning

confidence: 99%

“…We previously demonstrated that Th9-like MAIT cells are enriched in gastric tissue and revealed the positive correlation of Th9-producing MAIT cells with disease progression ( 4 ). We also reported that H. pylori -associated antigens induced the Th1 and Th17 response of gastric CD4 + T cells ( 5 ). These observations indicate the tight interactions between H. pylori and the different subsets of immune cells and elements in the mucosal tissue, which may contribute to inflammatory response and mucosal pathology.…”

Section: Introductionmentioning

confidence: 92%

GITR Promotes the Polarization of TFH-Like Cells in Helicobacter pylori-Positive Gastritis

Ming¹,

Yin²,

Li³

et al. 2021

Front. Immunol.

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Gastric CD4+T cells contribute to Helicobacter pylori (H. pylori)-induced gastritis by amplifying mucosal inflammation and exacerbating mucosal injuries. However, the pathogenic CD4+ T cell subset involved in gastritis and the potential regulators are still unclear. Here we identified an IL-21-producing gastric CD4+T cell subset, which exhibited tissue-resident CXCR5−BTLA−PD-1hi TFH-like phenotype in H. pylori-positive gastritis patients. Meanwhile, we identified glucocorticoid-induced tumor necrosis factor receptor (GITR) as an important regulator to facilitate IL-21 production by CD4+T cells and accelerate mucosal inflammation in gastritis patients with H. pylori infection. Moreover, GITR expression was increased in gastric CD4+T cells of gastritis patients compared to healthy controls, along with the upregulated expression of its ligand GITRL in mucosal macrophages (Mϕ) of gastritis patients. Further observations showed that the activation of GITR/GITRL signal promoted the IL-21 production of CD4+T cells via the STAT3 pathway. Besides this, IL-21 from CD4+T cells induced the proliferation of B cell and promoted the production of inflammatory cytokines IL-1β and IL-6 and chemokines MIP-3α and CCL-25 as well as matrix metalloproteinase (MMP)-3 and MMP-9 by human gastric epithelial cells, suggesting the facilitating effect of IL-21-producing CD4+T cells on mucosal inflammation and injuries. Taking these data together, we revealed that GITR/GITRL signal promoted the polarization of mucosal IL-21-producing CD4+T cells in H. pylori-positive gastritis, which may provide therapeutic strategies for the clinical treatment of H. pylori-induced gastritis.

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“…aEb7-expressing cells are able to interact with epithelial (E-) cadherin expressed by intestinal epithelial cells (IECs) and may thereby be retained in the tissue (113). Furthermore, evidence from cancer and gastritis research suggests that this interaction serves as a costimulatory factor for T cell receptor activation in CD8 + and CD4 + T cells, respectively (114)(115)(116)(117). Despite CD103 expression being associated with a Treg phenotype in mice (118)(119)(120), recent evidence suggests a pro-inflammatory Th1, Th17 and Th1/17 phenotype for aEb7 + CD4 + T cells with reduced expression of Treg markers in the large intestine of UC patients, proposing a role for these cells in disease pathobiology (121).…”

Section: Integrin Blockade Beyond α4β7-blockade -Interfering With Retentionmentioning

confidence: 99%

Targeting Immune Cell Trafficking – Insights From Research Models and Implications for Future IBD Therapy

et al. 2021

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Inflammatory bowel diseases (IBDs), including Crohn’s disease (CD) and ulcerative colitis (UC) are multifactorial diseases with still unknown aetiology and an increasing prevalence and incidence worldwide. Despite plentiful therapeutic options for IBDs, the lack or loss of response in certain patients demands the development of further treatments to tackle this unmet medical need. In recent years, the success of the anti-α4β7 antibody vedolizumab highlighted the potential of targeting the homing of immune cells, which is now an important pillar of IBD therapy. Due to its complexity, leukocyte trafficking and the involved molecules offer a largely untapped resource for a plethora of potential therapeutic interventions. In this review, we aim to summarise current and future directions of specifically interfering with immune cell trafficking. We will comment on concepts of homing, retention and recirculation and particularly focus on the role of tissue-derived chemokines. Moreover, we will give an overview of the mode of action of drugs currently in use or still in the pipeline, highlighting their mechanisms and potential to reduce disease burden.

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CD103 Promotes the Pro-inflammatory Response of Gastric Resident CD4+ T Cell in Helicobacter pylori-Positive Gastritis

Cited by 10 publications

References 61 publications

OX40L/OX40 Signal Promotes IL-9 Production by Mucosal MAIT Cells During Helicobacter pylori Infection

OX40L/OX40 Signal Promotes IL-9 Production by Mucosal MAIT Cells During Helicobacter pylori Infection

GITR Promotes the Polarization of TFH-Like Cells in Helicobacter pylori-Positive Gastritis

Targeting Immune Cell Trafficking – Insights From Research Models and Implications for Future IBD Therapy

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