Increased IL-17A Serum Levels and Gastric Th17 Cells in Helicobacter pylori-Infected Patients with Gastric Premalignant Lesions

Bella, Chiara Della; D’Elios, Sofia; Coletta, Sara; Benagiano, Marisa; Azzurri, Annalisa; Cianchi, Fabio; Bernard, Marina de; D’Elios, Mario Milco

doi:10.3390/cancers15061662

Cited by 8 publications

(1 citation statement)

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“…These data, together with the previous findings on the pathologic functions of IL-17A and T H 17 cells during H. pylori infection [ 37 ], emphasizes the important determinants of IL-17A from T H 17 cells for ANGPTL4 induction within the gastric mucosa. More importantly, increased IL-17A serum levels and gastric T H 17 cells have been found in H. pylori -infected patients with gastric premalignant lesions [ 38 ], and H. pylori lipoprotein HP1454 can regulate T cell response by shaping T cell receptor signaling [ 39 ], together suggesting that T H 17 cell responses induced by H. pylori -associated factors contribute to progressive pathological roles within the gastric mucosa.…”

Section: Discussionmentioning

confidence: 99%

Helicobacter pylori -Induced Angiopoietin-Like 4 Promotes Gastric Bacterial Colonization and Gastritis

Xie,

You,

Chen

et al. 2024

Research

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Helicobacter pylori infection is characterized as progressive processes of bacterial persistence and chronic gastritis with features of infiltration of mononuclear cells more than granulocytes in gastric mucosa. Angiopoietin-like 4 (ANGPTL4) is considered a double-edged sword in inflammation-associated diseases, but its function and clinical relevance in H. pylori -associated pathology are unknown. Here, we demonstrate both pro-colonization and pro-inflammation roles of ANGPTL4 in H. pylori infection. Increased ANGPTL4 in the infected gastric mucosa was produced from gastric epithelial cells (GECs) synergistically induced by H. pylori and IL-17A in a cagA -dependent manner. Human gastric ANGPTL4 correlated with H. pylori colonization and the severity of gastritis, and mouse ANGPTL4 from non-bone marrow-derived cells promoted bacteria colonization and inflammation. Importantly, H. pylori colonization and inflammation were attenuated in Il17a −/− , Angptl4 −/− , and Il17a −/− Angptl4 −/− mice. Mechanistically, ANGPTL4 bound to integrin αV (ITGAV) on GECs to suppress CXCL1 production by inhibiting ERK, leading to decreased gastric influx of neutrophils, thereby promoting H. pylori colonization; ANGPTL4 also bound to ITGAV on monocytes to promote CCL5 production by activating PI3K–AKT–NF-κB, resulting in increased gastric influx of regulatory CD4 + T cells (T regs ) via CCL5–CCR4-dependent migration. In turn, ANGPTL4 induced T reg proliferation by binding to ITGAV to activate PI3K–AKT–NF-κB, promoting H. pylori -associated gastritis. Overall, we propose a model in which ANGPTL4 collectively ensures H. pylori persistence and promotes gastritis. Efforts to inhibit ANGPTL4-associated pathway may prove valuable strategies in treating H. pylori infection.

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Section: Discussionmentioning

confidence: 99%