Inflammation-Induced Th17 Cells Synergize with the Inflammation-Trained Microbiota to Mediate Host Resiliency Against...

Area of Science:

• Immunology
• Microbiology
• Gastroenterology

Background:

• Inflammation can induce pathogenic Th17 cells and dysbiosis, potentially worsening inflammatory bowel disease (IBD).
• Existing IBD models often lack regulatory pathways, making it unclear if inflammation can also generate protective Th17 cells.

Purpose of the Study:

• To investigate whether inflammation can induce protective Th17 cells.
• To determine the role of the microbiota in inflammation-induced protection.

Main Methods:

• Mice were infected with Citrobacter rodentium (Cr) and treated with dextran sodium sulfate (DSS) to induce injury.
• Immune responses, cytokines, inflammation, and gut bacterial taxonomy were assessed using flow cytometry, qPCR, histology, and 16s sequencing.
• Fecal microbiota transfer and cell trafficking inhibitors were used to elucidate mechanisms of protection.

Main Results:

• Transient gastrointestinal (GI) Cr infection, but not systemic infection, conferred protection against subsequent intestinal injury.
• This protection was tissue-specific and associated with the expansion of intestinal Th17 cells with a tissue-resident memory (TRM) signature.
• Inflammation-induced Th17 cells and an "inflammation-trained" microbiota were essential for this protective effect.

Conclusions:

• Inflammation can generate protective Th17 TRM cells that, alongside an adapted microbiota, enhance host resilience to intestinal injury.
• These findings reveal heterogeneity within inflammation-induced Th17 cells, identifying protective subsets crucial for host defense.