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). [10.26508/lsa.201800229]

Mucosa-associated microbiota drives pathogenic functions in IBD-derived intestinal iNKT cells

C. Burrello
Primo
;
G. Pellegrino
Secondo
;
G. Lovati;A. Bertocchi;F. Boggio;F. Botti;M. Vecchi;M. Rescigno;F. Caprioli
Penultimo
;
2019-02-13

Abstract

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.
Settore MED/12 - Gastroenterologia
Settore BIO/13 - Biologia Applicata
Settore MED/04 - Patologia Generale
Settore BIO/19 - Microbiologia Generale
Settore MED/08 - Anatomia Patologica
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/626219
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