Title :

Il-7 receptor influences anti-tnf responsiveness and t cell gut homing in inflammatory bowel disease

Author(s) :

Belarif, Lyssia [Auteur]
OSE Immunotherapeutics [Nantes]
Danger, Richard [Auteur]
Institut de transplantation urologie-néphrologie [ITUN]
Kermarrec, Laetitia [Auteur]
The Enteric Nervous System in gut and brain disorders [U1235] [TENS]
Nerriere-Daguin, Veronique [Auteur]
Institut de transplantation urologie-néphrologie [ITUN]
Pengam, Sabrina [Auteur]
OSE Immunotherapeutics [Nantes]
Durand, Tony [Auteur]
The Enteric Nervous System in gut and brain disorders [U1235] [TENS]
Mary, Caroline [Auteur]
OSE Immunotherapeutics [Nantes]
Kerdreux, Elise [Auteur]
Centre Hospitalier Universitaire de Nantes = Nantes University Hospital [CHU Nantes]
Gauttier, Vanessa [Auteur]
OSE Immunotherapeutics [Nantes]
Kucik, Aneta [Auteur]
Thepenier, Virginie [Auteur]
OSE Immunotherapeutics [Nantes]
Martin, Jerome C. [Auteur]
Chang, Christie [Auteur]
Rahman, Adeeb [Auteur]
Guen, Nina Salabert-Le [Auteur]
Centre de Recherche en Transplantation et Immunologie [U1064 Inserm - CRTI]
Braudeau, Cecile [Auteur]
Centre de Recherche en Transplantation et Immunologie [U1064 Inserm - CRTI]
Abidi, Ahmed [Auteur]
Centre de Recherche en Transplantation et Immunologie [U1064 Inserm - CRTI]
David, Gregoire [Auteur]
The Enteric Nervous System in gut and brain disorders [U1235] [TENS]
Malard, Florent [Auteur]
Centre de Recherche en Transplantation et Immunologie [U1064 Inserm - CRTI]
Takoudju, Celine [Auteur]
The Enteric Nervous System in gut and brain disorders [U1235] [TENS]
Martinet, Bernard [Auteur]
Centre de Recherche en Transplantation et Immunologie [U1064 Inserm - CRTI]
Gerard, Nathalie [Auteur]
Centre de Recherche en Transplantation et Immunologie [U1064 Inserm - CRTI]
Neveu, Isabelle [Auteur]
The Enteric Nervous System in gut and brain disorders [U1235] [TENS]
Neunlist, Michel [Auteur]
The Enteric Nervous System in gut and brain disorders [U1235] [TENS]
Coron, Emmanuel [Auteur]
The Enteric Nervous System in gut and brain disorders [U1235] [TENS]
Macdonald, Thomas T. [Auteur]
Desreumaux, Pierre [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Mai, Hoa-Le [Auteur]
Centre de Recherche en Transplantation et Immunologie [U1064 Inserm - CRTI]
Le Bas-Bernardet, Stephanie [Auteur]
Centre de Recherche en Transplantation et Immunologie [U1064 Inserm - CRTI]
Mosnier, Jean-Francois [Auteur]
Université de Nantes [UN]
Merad, Miriam [Auteur]
Josien, Regis [Auteur]
Centre de Recherche en Transplantation et Immunologie [U1064 Inserm - CRTI]
Brouard, Sophie [Auteur]
Centre de Recherche en Transplantation et Immunologie [U1064 Inserm - CRTI]
Soulillou, Jean-Paul [Auteur]
Centre de Recherche en Transplantation et Immunologie [U1064 Inserm - CRTI]
Blancho, Gilles [Auteur]
Centre de Recherche en Transplantation et Immunologie [U1064 Inserm - CRTI]
Bourreille, Arnaud [Auteur]
The Enteric Nervous System in gut and brain disorders [U1235] [TENS]
Naveilhan, Philippe [Auteur]
The Enteric Nervous System in gut and brain disorders [U1235] [TENS]
Vanhove, Bernard [Auteur]
OSE Immunotherapeutics [Nantes]
Poirier, Nicolas [Auteur]
OSE Immunotherapeutics [Nantes]

Journal title :

The Journal of clinical investigation

Abbreviated title :

J. Clin. Invest.

Volume number :

129

Pages :

1910-1925

Publication date :

2019-05-01

ISSN :

1558-8238

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

It remains unknown what causes inflammatory bowel disease (IBD), including signaling networks perpetuating chronic gastrointestinal inflammation in Crohn's disease (CD) and ulcerative colitis (UC), in humans. According to ...
Show more >It remains unknown what causes inflammatory bowel disease (IBD), including signaling networks perpetuating chronic gastrointestinal inflammation in Crohn's disease (CD) and ulcerative colitis (UC), in humans. According to an analysis of up to 500 patients with IBD and 100 controls, we report that key transcripts of the IL-7 receptor (IL-7R) pathway are accumulated in inflamed colon tissues of severe CD and UC patients not responding to either immunosuppressive/corticosteroid, anti-TNF, or anti-α4β7 therapies. High expression of both IL7R and IL-7R signaling signature in the colon before treatment is strongly associated with nonresponsiveness to anti-TNF therapy. While in mice IL-7 is known to play a role in systemic inflammation, we found that in humans IL-7 also controlled α4β7 integrin expression and imprinted gut-homing specificity on T cells. IL-7R blockade reduced human T cell homing to the gut and colonic inflammation in vivo in humanized mouse models, and altered effector T cells in colon explants from UC patients grown ex vivo. Our findings show that failure of current treatments for CD and UC is strongly associated with an overexpressed IL-7R signaling pathway and point to IL-7R as a relevant therapeutic target and potential biomarker to fill an unmet need in clinical IBD detection and treatment.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

CHU Lille
Inserm
Université de Lille

Collections :

• Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286

Submission date :

2024-01-30T10:27:00Z
2024-03-28T12:12:17Z