Expression pattern and functional role of DNAM-1 family co-receptors on mucosal and peripheral blood T cell populations of pediatric subjects and Inflammatory Bowel Diseases (IBD) patients.

PURPOSE: To investigate the role of DNAM-1 (activating) and Tigit (inhibitory) co-receptors on circulating and mucosal “innate-like” (CD56+ and CD4-CD8-) and “classical” (CD4+ and CD8+) T cell populations, and their potential role in Inflammatory Bowel Disease (IBD) pathogenesis. METHODS: We analysed the distribution of DNAM-1 family members on peripheral blood and mucosal (colon biopsy) T cell populations cells from pediatric IBD patients and age-matched controls, with a multiparameter citofluorimetric approach. RESULTS: Peripheral blood “classical” and “innate-like” T cell populations differently express DNAM-1 family co-receptors; within each subset, mucosa addressin (CCR6+ or CD103+)-expressing cells display a distinct profile, as compared to negative ones. DNAM-1 expression positively correlates with an enhanced capability to produce IFN γ, within both “classical” and “innate-like” peripheral blood T cells; a comparable enrichment in the functional capability is observed in Tigit

PURPOSE: To investigate the role of DNAM-1 (activating) and Tigit (inhibitory) co-receptors on circulating and mucosal “innate-like” (CD56+ and CD4-CD8-) and “classical” (CD4+ and CD8+) T cell populations, and their potential role in Inflammatory Bowel Disease (IBD) pathogenesis. METHODS: We analysed the distribution of DNAM-1 family members on peripheral blood and mucosal (colon biopsy) T cell populations cells from pediatric IBD patients and age-matched controls, with a multiparameter citofluorimetric approach. RESULTS: Peripheral blood “classical” and “innate-like” T cell populations differently express DNAM-1 family co-receptors; within each subset, mucosa addressin (CCR6+ or CD103+)-expressing cells display a distinct profile, as compared to negative ones. DNAM-1 expression positively correlates with an enhanced capability to produce IFN γ, within both “classical” and “innate-like” peripheral blood T cells; a comparable enrichment in the functional capability is observed in Tigit+ “classical”, but not “innate-like” T cells. The expression pattern of DNAM-1 and Tigit strikingly differs between tissue and peripheral T cell compartments: DNAM-1+ cells are strongly reduced on all analyzed mucosal subsets, whereas the frequency of Tigit+ cells is significatively augmented on mucosal CD4+ and DN, but not on CD8+ T cells; moreover, Tigit surface levels are significatively reduced on mucosal T cells of active IBD lesions. DISCUSSION & CONCLUSIONS: Our results show that DNAM-family co-receptors are differently expressed on distinct T cell subsets; moreover, coreceptor expression strikingly differs between a relatively ligand-free environment (peripheral blood), and a ligand-rich tissue (intestinal mucosa). Ligand presence in the environment may also influence coreceptor levels in inflamed vs non-inflamed mucosa populations. These results may underline a primary role for DNAM-1 family coreceptors in the fine-tuning of mucosal immunity and in IBD pathogenesis.