GUT MICROBIOTA CROSSTALK WITH CONVENTIONAL AND NON-CONVENTIONAL T CELLS: A GAME OF MANY PLAYERS.

The presence of microbial commensals in the gut requires the establishment of a complex network of reciprocal interactions between the microbiota and the host immune system to allow nutrient absorption while preventing undesired mucosal immune responses. Despite these homeostatic mechanisms, during intestinal inflammation alterations of the microbiota composition, namely dysbiosis, trigger abnormal immune responses. Here, we aimed at investigating the functional crosstalk between gut microbiota and the mucosal immune system during inflammation and upon induction of microbial dysbiosis. We observed that inflammation-induced and antibiotic-driven types of dysbiosis are phenotypically and functionally modifying CD4+ T and iNKT cells activity. Moreover, during intestinal inflammation, the experimental manipulation of the microbiota community through Faecal Microbiota Transplantation (FMT) reduces colonic inflammation and initiates the restoration of intestinal homeostasis through the induction of IL-10 production by immune cells. Further, we performed a comprehensive analysis on intestinal iNKT cells isolated from surgical specimens of active Inflammatory Bowel Disease (IBD) patients and non-IBD donors. We report that the exposure to mucosa-associated microbiota drives iNKT cell pro-inflammatory activation, inducing direct pathogenicity against the intestinal epithelium. Collectively, we provided solid evidence that a strict crosstalk between the gut microbiota and the intestinal conventional and non-conventional T cells exists. Antibiotic-associated dysbiosis has immunostimulatory functions. Moreover, FMT can therapeutically control intestinal experimental colitis and this poses FMT as a valuable therapeutic option in immune-related pathologies. In addition, we generated fundamental knowledge about the pathogenic functions exerted by human intestinal iNKT cells upon the interaction with mucosa-associated microbiota communities.