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De-regulated T-cell activation and functions are pivotal in the orchestration of immune-mediated tissue damage in IBD. We investigated the role of DNAM-1 (co-activating)/TIGIT (co-inhibitory)/ligand axis in the regulation of T-cell functions and its involvement in IBD pathogenesis. We show that DNAM-1 and TIGIT display a peculiar expression pattern on gut mucosa T-cell populations, in a microenvironment where their shared ligands (PVR and Nectin-2) are physiologically present. Moreover, DNAM-1 family receptor/ligand system is perturbed in IBD lesions, in a disease activity-dependent manner. The expression profile of CCR6 and CD103 mucosa addressins suggests that microenvironment-associated factors, rather than skewed recruitment of circulating T-cell populations, play a more relevant role in supporting the establishment of DNAM-1 and TIGIT expression pattern in mucosal T-cell populations, and may explain its alteration in IBD. Although both co-receptors mark functionally competent T cells, DNAM-1 and TIGIT segregate on T cells endowed with different proliferative potential. Moreover, their opposing role in regulating T-cell proliferation exquisitely depends on ligand availability. All together, our data propose a role for DNAM-1 and TIGIT in regulating mucosal T-cell activation and immune homeostasis, and highlight the involvement of an imbalance of this system in IBD.

De-regulated T-cell activation and functions are pivotal in the orchestration of immune-mediated tissue damage in IBD. We investigated the role of DNAM-1 (co-activating)/TIGIT (co-inhibitory)/ligand axis in the regulation of T-cell functions and its involvement in IBD pathogenesis. We show that DNAM-1 and TIGIT display a peculiar expression pattern on gut mucosa T-cell populations, in a microenvironment where their shared ligands (PVR and Nectin-2) are physiologically present. Moreover, DNAM-1 family receptor/ligand system is perturbed in IBD lesions, in a disease activity-dependent manner. The expression profile of CCR6 and CD103 mucosa addressins suggests that microenvironment-associated factors, rather than skewed recruitment of circulating T-cell populations, play a more relevant role in supporting the establishment of DNAM-1 and TIGIT expression pattern in mucosal T-cell populations, and may explain its alteration in IBD. Although both co-receptors mark functionally competent T cells, DNAM-1 and TIGIT segregate on T cells endowed with different proliferative potential. Moreover, their opposing role in regulating T-cell proliferation exquisitely depends on ligand availability. All together, our data propose a role for DNAM-1 and TIGIT in regulating mucosal T-cell activation and immune homeostasis, and highlight the involvement of an imbalance of this system in IBD.

Patients (pts) with eosinophilic esophagitis (EoE), a chronic immune-mediated disorder, may exhibit symptoms of disturbed food transit (i.e. dysphagia, impaction) or mimicking gastro-oesophageal reflux (GOR). We aimed at characterizing in EoE pts the intra-esophageal pH pattern with 24-h multichannel intraluminal impedance (MII-pH) as well as the esophageal motility with high-resolution manometry (EHRM) during a 30 month period we studied 57 patients (pts), median age 11 years (range: 7–16): 25 with EoE, diagnosed according to widely agreed criteria (JPGN 2014;58:107–18; ESPGHAN guidelines) and 32 with GOR disease (GORD). All underwent esophagogastro-duodenoscopy, MII-pH and EHRM. The pH-MII and data analysis were done according to ESPGHAN EURO-PIG protocol (JPGN 2012;55:230–4); variables analysed: reflux index, symptom index, number and type of liquid reflux, number of long lasting reflux episodes, correlation symptom-reflux. The test was diagnostic of GORD if at least = 2 of the previous variables were positive. The EHRM was performed with water perfused catheters and swallow contractile patterns categorized using criteria recently reported by a paediatric group (Am?J Gastroenterol 2010;105:460–7). Several motility variables were analysed: esophago-gastric junction (EGJ) morphology, end-expiratory and end-inspiratory EGJ pressure, distal contractile integral (DCI), pressurization front velocity (cm/s), peristaltic propagation pattern. An abnormal MII-pH profile was markedly more common in GORD pts (27; 84.37%) than in EoE pts (4; 16%; p?