RT Journal Article
SR Electronic
T1 Mucosa-associated microbiota drives pathogenic functions in IBD-derived intestinal iNKT cells
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e201800229
DO 10.26508/lsa.201800229
VO 2
IS 1
A1 Burrello, Claudia
A1 Pellegrino, Gabriella
A1 Giuffrè, Maria Rita
A1 Lovati, Giulia
A1 Magagna, Ilaria
A1 Bertocchi, Alice
A1 Cribiù, Fulvia Milena
A1 Boggio, Francesca
A1 Botti, Fiorenzo
A1 Trombetta, Elena
A1 Porretti, Laura
A1 Di Sabatino, Antonio
A1 Vecchi, Maurizio
A1 Rescigno, Maria
A1 Caprioli, Flavio
A1 Facciotti, Federica
YR 2019
UL http://www.life-science-alliance.org/content/2/1/e201800229.abstract
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.