PT - JOURNAL ARTICLE AU - Burrello, Claudia AU - Pellegrino, Gabriella AU - Giuffrè, Maria Rita AU - Lovati, Giulia AU - Magagna, Ilaria AU - Bertocchi, Alice AU - Cribiù, Fulvia Milena AU - Boggio, Francesca AU - Botti, Fiorenzo AU - Trombetta, Elena AU - Porretti, Laura AU - Di Sabatino, Antonio AU - Vecchi, Maurizio AU - Rescigno, Maria AU - Caprioli, Flavio AU - Facciotti, Federica TI - Mucosa-associated microbiota drives pathogenic functions in IBD-derived intestinal iNKT cells AID - 10.26508/lsa.201800229 DP - 2019 Feb 01 TA - Life Science Alliance PG - e201800229 VI - 2 IP - 1 4099 - https://www.life-science-alliance.org/content/2/1/e201800229.short 4100 - https://www.life-science-alliance.org/content/2/1/e201800229.full SO - Life Sci. Alliance2019 Feb 01; 2 AB - Inflammatory bowel disease (IBD) pathogenesis has been linked to the aberrant activation of the Gut-associated lymphoid tissues against components of the intestinal microbiota. Although the contribution of CD4+ T helper cells to inflammatory processes is being increasingly acknowledged, the functional engagement of human invariant natural killer T (iNKT) cells is still poorly defined. Here, we evaluated the functional characteristics of intestinal iNKT cells during IBD pathogenesis and to exploit the role of mucosa-associated microbiota recognition in triggering iNKT cells’ pro-inflammatory responses in vivo. Lamina propria iNKT cells, isolated from surgical specimens of active ulcerative colitis and Crohn’s disease patients and non-IBD donors, were phenotypically and functionally analyzed ex vivo, and stable cell lines and clones were generated for in vitro functional assays. iNKT cells expressing a pro-inflammatory cytokine profile were enriched in the lamina propria of IBD patients, and their exposure to the mucosa-associated microbiota drives pro-inflammatory activation, inducing direct pathogenic activities against the epithelial barrier integrity. These observations suggest that iNKT cell pro-inflammatory functions may contribute to the fuelling of intestinal inflammation in IBD patients.