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.
Mucosa-associated microbiota drives pathogenic functions in IBD-derived intestinal iNKT cells / C. Burrello, G. Pellegrino, M.R. Giuffrè, G. Lovati, I. Magagna, A. Bertocchi, F.M. Cribiù, F. Boggio, F. Botti, E. Trombetta, L. Porretti, A. Di Sabatino, M. Vecchi, M. Rescigno, F. Caprioli, F. Facciotti. - In: LIFE SCIENCE ALLIANCE. - ISSN 2575-1077. - 2:1(2019 Feb 13).
|Titolo:||Mucosa-associated microbiota drives pathogenic functions in IBD-derived intestinal iNKT cells|
BURRELLO, CLAUDIA (Primo)
PELLEGRINO, GABRIELLA (Secondo)
CAPRIOLI, FLAVIO ANDREA (Penultimo)
|Settore Scientifico Disciplinare:||Settore MED/12 - Gastroenterologia|
Settore BIO/13 - Biologia Applicata
Settore MED/04 - Patologia Generale
Settore BIO/19 - Microbiologia Generale
Settore MED/08 - Anatomia Patologica
|Data di pubblicazione:||13-feb-2019|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.26508/lsa.201800229|
|Appare nelle tipologie:||01 - Articolo su periodico|