IL-17RA-Mediated Epithelial Cell Activity Prevents Severe Inflammatory Response to Helicobacter pylori Infection

Area of Science:

• Immunology
• Gastroenterology
• Microbiology

Background:

• Helicobacter pylori infection causes stomach inflammation and increases gastric cancer risk.
• Interleukin-17 (IL-17) pathway, particularly IL-17 receptor A (IL-17RA), plays a role in immune responses.
• The specific role of IL-17RA in gastric epithelial cells during H. pylori infection is not fully understood.

Purpose of the Study:

• To investigate the role of IL-17RA signaling in gastric epithelial cells in response to H. pylori infection.
• To determine if epithelial IL-17RA deficiency exacerbates inflammation and immune responses.

Main Methods:

• Utilized genetically modified mice (Foxa3creIl17rafl/fl) with epithelial-specific deletion of IL-17RA (Il17raΔGI-Epi) and control mice (Il17rafl/fl).
• Infected mice with H. pylori and analyzed gastric inflammation, immune cell infiltration, and gene expression.
• Measured IgA levels in gastric washes and assessed T follicular helper/B cell axis activation.

Main Results:

• Mice lacking epithelial IL-17RA (Il17raΔGI-Epi) exhibited increased gastric inflammation compared to controls.
• Despite reduced Pigr expression, IgA levels increased in gastric washes, indicating enhanced T follicular helper/B cell activation.
• Gene expression analysis revealed significantly heightened acute and chronic inflammatory responses in Il17raΔGI-Epi mice.
• Fibroblast-derived chemokines in response to IL-17 may contribute to H. pylori-induced inflammation.

Conclusions:

• Epithelial IL-17RA signaling is crucial for protecting against severe inflammation in H. pylori infection.
• Deficiency in epithelial IL-17RA leads to chronic inflammation and hyperactivation of the Th17/T follicular helper/B cell axis.
• Fibroblasts may contribute to H. pylori-induced inflammation via IL-17-mediated chemokine production.