Summary contentEducational objective:
- To analyse Th17 plasticity in T-cell transfer colitis mouse model, and correlate this with the microbiota composition.
- To understand whether antibiotics affect Th17 plasticity through microbiota-dependent processes.
Summary. During Inflammatory Bowel Disease (IBD), CD4+ effector T cells are main mediators of the tissue damage. Among them, Th17 cells strongly contribute to the inflammatory response. Interestingly, our lab previously showed that Th17 cells can convert into regulatory T cells, thereby controlling inflammation. However, the forces controlling the plasticity of T cells during IBD remain largely unknown. Our aim is to understand, how CD4+ T-cell plasticity can be modulated from a pro-inflammatory towards an anti-inflammatory profile during IBD. In this regard, both Th17 and Foxp3 regulatory T cells can recognize microbiota-antigens. Moreover, changes in the microbiota are commonly observed in IBD. Therefore, we hypothesize that the microbiota might be a key candidate to modulate T-cell plasticity. To address our goal, T-cell transfer mouse IBD model was performed by transferring CD4+ naïve T-cells into Rag1-/- mice. To study Th17 T-cell plasticity, we used as donors IL-17A Fate-mapping mice. Ciprofloxacin and metronidazole, antibiotics commonly given to IBD patients, were used to treat the mice. After T-cell transfer colitis induction, ciprofloxacin and metronidazole treatment ameliorated gut inflammation. In line with this, we observed a relative expansion of bacteria previously associated with beneficial IBD outcomes (e.g. Bifidobacterium). More interestingly, colon CD4+ T-cells showed an increased conversion from Th17 towards a Foxp3+ Treg profile (Foxp3ExTh17)(p=0.03).