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

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 functiona...

Full description

Saved in:
Bibliographic Details
Published in:Life science alliance 2019-02, Vol.2 (1), p.e201800229
Main Authors: Burrello, Claudia, Pellegrino, Gabriella, Giuffrè, Maria Rita, Lovati, Giulia, Magagna, Ilaria, Bertocchi, Alice, Cribiù, Fulvia Milena, Boggio, Francesca, Botti, Fiorenzo, Trombetta, Elena, Porretti, Laura, Di Sabatino, Antonio, Vecchi, Maurizio, Rescigno, Maria, Caprioli, Flavio, Facciotti, Federica
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Animals
Caco-2 Cells
CD4 Antigens - metabolism
Clone Cells - metabolism
Coculture Techniques
Colitis, Ulcerative - chemically induced
Colitis, Ulcerative - microbiology
Colitis, Ulcerative - pathology
Colitis, Ulcerative - surgery
Crohn Disease - microbiology
Crohn Disease - surgery
Cytokines - metabolism
Dextran Sulfate - pharmacology
Disease Models, Animal
Female
Gastrointestinal Microbiome
Humans
Inflammation - immunology
Inflammation - metabolism
Intestinal Mucosa - immunology
Intestinal Mucosa - microbiology
Lymphocyte Activation - immunology
Male
Mice
Mice, Inbred C57BL
Middle Aged
Natural Killer T-Cells - immunology
Natural Killer T-Cells - metabolism
NK Cell Lectin-Like Receptor Subfamily B - metabolism
Phenotype
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2575-1077
2575-1077
DOI:10.26508/LSA.201800229