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

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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.

Original languageEnglish
Article numbere201800229
JournalLife Science Alliance
Volume2
Issue number1
DOIs
Publication statusPublished - Feb 2019

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Natural Killer T-Cells
T-cells
inflammatory bowel disease
Microbiota
natural killer cells
Inflammatory Bowel Diseases
mucosa
Mucous Membrane
T-lymphocytes
laminae (animals)
Chemical activation
pathogenesis
inflammation
Fueling
Lymphoid Tissue
Helper-Inducer T-Lymphocytes
Crohn disease
Ulcerative Colitis
Crohn Disease
colitis

Cite this

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title = "Mucosa-associated microbiota drives pathogenic functions in IBD-derived intestinal iNKT cells",
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.",
author = "Claudia Burrello and Gabriella Pellegrino and Giuffr{\`e}, {Maria Rita} and Giulia Lovati and Ilaria Magagna and Alice Bertocchi and Cribi{\`u}, {Fulvia Milena} and Francesca Boggio and Fiorenzo Botti and Elena Trombetta and Laura Porretti and {Di Sabatino}, Antonio and Maurizio Vecchi and Maria Rescigno and Flavio Caprioli and Federica Facciotti",
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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

N1 - © 2019 Burrello et al.

PY - 2019/2

Y1 - 2019/2

N2 - 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.

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.

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