Programmed Death Ligand 1-Expressing Classical Dendritic Cells MitigateHelicobacter-Induced Gastritis

Area of Science:

• Immunology
• Gastroenterology
• Microbiology

Background:

• Helicobacter pylori infection causes persistent colonization in the gastric mucosa by modulating local immune responses.
• Programmed cell death ligand 1 (PD-L1) is implicated in immune modulation during H. pylori infection, but its specific cellular sources and functions in gastritis remain unclear.

Purpose of the Study:

• To elucidate the role of PD-L1-expressing immune cells in Helicobacter-induced gastritis.
• To investigate the function of the PD-1/PD-L1 pathway in gastric immune modulation during H. pylori infection.

Main Methods:

• Utilized mouse models with PD-L1 blockade or deficiency, and dendritic cell (DC)-specific depletions (Flt3-/-, Zbtb46-DTR, BDCA2-DTR) in Helicobacter-infected mice.
• Employed flow cytometry and immunofluorescence staining to identify PD-L1-expressing immune cells in gastric tissues.
• Analyzed human gastric tissues using multiplexed immunohistochemistry to assess PD-L1-expressing DCs and their correlation with H. pylori infection.

Main Results:

• Blocking PD-L1 aggravated Helicobacter-induced gastritis and mucosal metaplasia.
• Gastric classical DCs were the primary immune cells expressing PD-L1 and co-localized with T cells in gastritis lesions.
• DC-deficient mice exhibited exacerbated gastritis with increased T-cell and neutrophil infiltration but reduced bacterial loads.

Conclusions:

• The PD-1/PD-L1 pathway, particularly involving gastric DCs, plays a crucial role in immune modulation.
• This pathway protects the gastric mucosa from excessive inflammation while permitting persistent Helicobacter colonization.