TY - JOUR AU - Belarif, Lyssia AU - Danger, Richard AU - Kermarrec, Laetitia AU - Nerrière-Daguin, Véronique AU - Pengam, Sabrina AU - Durand, Tony AU - Mary, Caroline AU - Kerdreux, Elise AU - Gauttier, Vanessa AU - Kucik, Aneta AU - Thepenier, Virginie AU - Martin, Jerome C. AU - Chang, Christie AU - Rahman, Adeeb AU - Guen, Nina Salabert-Le AU - Braudeau, Cécile AU - Abidi, Ahmed AU - David, Grégoire AU - Malard, Florent AU - Takoudju, Celine AU - Martinet, Bernard AU - Gérard, Nathalie AU - Neveu, Isabelle AU - Neunlist, Michel AU - Coron, Emmanuel AU - MacDonald, Thomas T. AU - Desreumaux, Pierre AU - Mai, Hoa-Le AU - Le Bas-Bernardet, Stephanie AU - Mosnier, Jean-François AU - Merad, Miriam AU - Josien, Régis AU - Brouard, Sophie AU - Soulillou, Jean-Paul AU - Blancho, Gilles AU - Bourreille, Arnaud AU - Naveilhan, Philippe AU - Vanhove, Bernard AU - Poirier, Nicolas T1 - IL-7 receptor influences anti-TNF responsiveness and T cell gut homing in inflammatory bowel disease PY - 2019/05/01/ AB - 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. JF - The Journal of Clinical Investigation JA - J Clin Invest SN - 0021-9738 DO - 10.1172/JCI121668 VL - 129 IS - 5 UR - https://doi.org/10.1172/JCI121668 SP - 1910 EP - 1925 PB - The American Society for Clinical Investigation ER -