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

• Published in: Cellular and molecular gastroenterology and hepatology Vol. 18; no. 1; pp. 133 - 153
• Main Authors: Pabois, Julie, Durand, Tony, Le Berre, Catherine, Filippone, Rhiannon T., Noël, Théo, Durieu, Emilie, Bossard, Céline, Bruneau, Sarah, Rolli-Derkinderen, Malvyne, Nurgali, Kulmira, Neunlist, Michel, Bourreille, Arnaud, Neveu, Isabelle, Naveilhan, Philippe
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2024; Philadelphia, PA : American Gastroenterological Association; Elsevier
• Subjects: Chronic Colitis Mouse Model; Gastroenterology and Hepatology; Glial Cells; Life Sciences; Lifitegrast; Original Research; Plexitis; Plexitis; Lcn-2; TCR; TNFα; LMMP; IBD; ICAM-1; ENS; LPS; WT; Chronic Colitis Mouse Model; CMMC; PBS; IL; LFA-1; Glial Cells; DAPI; CFSE; Ctrl; IT; MIF; PBMC; Lifitegrast; LG; Glia; tumor necrosis factor α; IL-1β/TNFα; carboxyfluorescein succinimidyl ester; 4',6-diamidino-2-phenylindole; lymphocyte function-associated antigen-1; phosphate-buffered saline; mean intensity of fluorescence; T-cell receptor; interleukin; colonic migrating motor complexes; intercellular adhesion molecule-1; longitudinal muscle-myenteric plexus; wild-type mice; lipopolysaccharides; enteric glial cells; control; inflammatory bowel disease; enteric nervous system; lipocalin-2; peripheral blood mononuclear cell
• ISSN: 2352-345X; 2352-345X
• DOI: 10.1016/j.jcmgh.2024.02.016

The 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. T 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. The 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 with controls (0.36 ± 0.08, P = .0007). Co-culture experiments showed that exposure to proinflammatory cytokines enhanced T-cell adhesion to glia and increased intercellular adhesion molecule-1 (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/lymphocyte function-associated antigen-1 (LFA-1) with lifitegrast reduced colitis severity and decreased T-cell infiltration in the myenteric plexus. Our 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. [Display omitted]