Role of ICAM-1 in the Adhesion of T Cells to Enteric Glia: Perspectives in the Formation of Plexitis in Crohn’s Disease

Abstract

Background & AimsThe presence of myenteric plexitis in the proximal resection margins is a predictive factor of early postoperative recurrence in Crohn’s disease. To decipher the mechanisms leading to their formation, T cell interactions with enteric neural cells were studied in vitro and in vivo. MethodsT cells close to myenteric neural cells were retrospectively quantified in ileocolonic resections from 9 control subjects with cancer and 20 patients with Crohn’s disease. The mechanisms involved in T cell adhesion were then investigated in co-cultures of T lymphocytes with enteric glial cells (glia). Finally, the implication of adhesion molecules in the development of plexitis and colitis was studied in vitro, but also in vivo in Winnie mice. ResultsThe mean number of T cells close to glia, but not neurons, was significantly higher in the myenteric ganglia of relapsing patients with Crohn’s disease (2.42+/-0.5) as compared to controls (0.36+/-0.08, p=0.0007). Co-culture experiments showed that exposure to pro-inflammatory cytokines enhanced T cell adhesion to glia and increased ICAM-1 expression in glia. We next demonstrated that T cell adhesion to glia was inhibited by an anti-ICAM-1 antibody. Finally, using the Winnie mouse model of colitis, we showed that the blockage of ICAM-1/ LFA-1 with lifitegrast reduced colitis severity and decreased T cell infiltration in the myenteric plexus. ConclusionsOur present work argues for a role of Glia-T cell interaction in the development of myenteric plexitis through the adhesion molecules ICAM-1/LFA-1, and suggests that deciphering the functional consequences of Glia-T cell interaction is important to understand the mechanisms implicated in the development and recurrence of Crohn’s disease.