Gastroenterology · 3 h ago
Indole–Trim21 pathway linked to Th17 overproduction in experimental colitis
In a series of mouse models of acute and chronic colitis, researchers investigated how gut microbial indole affects intestinal Th17 cells. They report that indole promotes Trim21 transcription through PKA and SP1, and that experimental approaches targeting this pathway or altering microbial tryptophan metabolism reduced colitis in mice.
- Indole promoted Trim21 transcription through PKA and SP1 in mice.
- Higher Th17-cell generation was linked to experimental colitis.
- Microbial and Trim21-targeting interventions reduced disease in mouse models.
Researchers used several mouse models of inflammatory bowel disease (IBD), including DSS- and TNBS-induced acute colitis and chronic colitis models, alongside molecular and multiomics analyses. They examined how microbial indole influences intestinal T helper-17 (Th17) cell generation and tested interventions in mice.
The study reports that indole strengthened the interaction between protein kinase A (PKA) and the transcription factor SP1, promoting SP1 activation and Trim21 transcription. Increased Trim21 was linked to degradation of Fbxw7 and excess Th17-cell generation. Tryptophan-rich feeding worsened IBD in the models, while colonization with Dubosiella newyorkensis shifted tryptophan metabolism toward kynurenine and alleviated disease. A CD4-targeted extracellular-vesicle approach inhibiting Trim21 also reduced Th17 generation and colitis.
These findings identify a proposed microbiota–indole–Trim21 mechanism and potential intervention targets, but the reported evidence is preclinical. The article does not provide sample sizes or effect estimates in the supplied text, and the mouse findings do not establish efficacy or safety in people with IBD.
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BMC Medicine: Indole induces intestinal T helper-17 cell overproduction during inflammatory bowel disease through PKA/SP1-mediated Trim21 transcription ↗This is an automated AI-condensed summary that has not yet been reviewed by an editor. Always consult the full item at the original source.