Th17-cell plasticity in Helicobacter hepaticus-induced intestinal inflammation

Area of Science:

• Immunology
• Microbiology
• Gastroenterology

Background:

• Bacterial-induced intestinal inflammation relies on interleukin-23 (IL-23) and involves CD4(+) T helper type 1 (Th1) and Th17 responses.
• The specific roles of Th1 and Th17 cells in the development and resolution of colitis are not fully understood.

Purpose of the Study:

• To investigate the dynamic interplay between Th1 and Th17 cells during Helicobacter hepaticus-induced colitis.
• To determine the phenotypic plasticity of Th17 cells in the context of bacterial gut inflammation.

Main Methods:

• Utilized IL-10(-/-) mice infected with Helicobacter hepaticus to model typhlocolitis.
• Analyzed CD4(+) T cell populations, including interferon-γ (IFN-γ)(+) and IL-17A(+) subsets, using flow cytometry and transcriptomic analysis.
• Employed IL-17A fate-reporter mice to track Th17 cell differentiation and plasticity.

Main Results:

• Helicobacter hepaticus infection led to increased frequencies of IFN-γ(+) and IFN-γ(+)IL-17A(+) CD4(+) T cells in the inflamed intestine.
• Th17 cells expressed IL-23R and showed a predisposition to adopt a Th1 program.
• A significant proportion of Th17 cells transitioned to an IFN-γ-producing phenotype (ex-Th17 cells) within 10 days post-infection.

Conclusions:

• Bacterial-induced Th17 cells in susceptible hosts can switch to a Th1 phenotype, characterized by IFN-γ production.
• This Th17 to Th1 cell plasticity, potentially via an IFN-γ(+)IL-17A(+) intermediate stage, contributes to intestinal pathology.
• Understanding this cellular plasticity is crucial for developing targeted therapies for inflammatory bowel diseases.