PROJECT TITLE: Targeting CD4+ T-cell plasticity in Inflammatory Bowel Diseases
© Andres Machicote
1. Background & aim of research
Inflammatory Bowel Diseases (IBD) are devastating diseases induced by a breakdown of gut homeostasis, in which CD4+ effector T cells are major mediators of the inflammatory response. Interestingly, CD4+ effector T cells can convert into regulatory T cells, thereby controlling inflammation. However, the forces driving this T-cell plasticity remain largely unexplored, especially in IBD patients. In this regard, changes in the microbiota that can induce different T-cell profiles are commonly observed during IBD. The present proposal aims to elucidate how CD4+ T-cell plasticity can be modulated from a pro-inflammatory towards an anti-inflammatory profile in IBD patients. Our hypothesis is that the microbiota may modulate T cells towards an anti- or pro-inflammatory profile. To address this issue, we aim to analyse T-cell plasticity in IBD patients and mouse IBD models, and to correlate our findings with the microbiota composition. Furthermore, we will study whether antibiotics commonly used to treat IBD affect T-cell plasticity through microbiota-dependent processes.