Inflammation induced T h 17 cells synergize with the inflammation-trained microbiota to mediate host-resiliency against intestinal injury
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Background and Aims
Inflammation can generate pathogenic T h 17 cells and cause a inflammatory dysbiosis. In the context of Inflammatory Bowel Disease (IBD) these inflammatory T h 17 cells and dysbiotic microbiota may perpetuate injury to intestinal epithelial cells (IECs). However, many models of IBD like T-cell transfer colitis and IL-10 -/- mice rely on the absence of regulatory pathways, so it is difficult to tell if inflammationcan also induce protective T h 17 cells.
Methods
We subjected C57BL6, RAG1 -/- or J H -/- mice to systemic or gastrointestinal (GI) Citrobacter rodentium ( Cr ). Mice were then subject to 2.5% dextran sodium sulfate to cause epithelial injury. Fecal microbiota transfer was performed by bedding transfer and co-housing. Flow cytometry, qPCR, 16s sequencing and histology were used to assess parameters.
Results
Transient inflammation with GI but not systemic Cr was protective from subsequent intestinal injury. This was replicated with sequential DSS collectively indicating that transient inflammation provides tissue-specific protection. Inflammatory T h 17 cells that have a tissue resident memory signature expanded in the intestine. Experiments with reconstituted RAG1 -/- , J H -/- mice and cell trafficking inhibitors showed that inflammation induced T h 17 cells were required for protection. Fecal microbiota transfer showed that the inflammation-trained microbiota was necessary for protection, likely by maintaining protective T h 17 cells in situ .
Conclusion
Inflammation can generate protective T h 17 cells which synergize with the inflammation-trained microbiota to provide host resiliency against subsequent injury, indicating that inflammation induced T h 17 tissue resident memory T cells are heterogenous and contain protective subsets.
