Critical role of CD6highCD4+ T cells in driving Th1/Th17 cell immune responses and mucosal inflammation in IBD.
J Crohns Colitis. 2018 Nov 03;:
Authors: Ma C, Wu W, Lin R, Ge Y, Zhang C, Sun S, Cong Y, Li X, Liu Z
Background and Aims: CD6 is a crucial regulator of T cell activation and implicated in the pathogenesis of multiple autoimmune diseases. ALCAM is the first identified endogenous ligand of CD6. We sought to investigate potential roles of CD6 in regulating intestinal mucosal inflammation of inflammatory bowel disease [IBD].
Methods: We analysed expression of CD6 and ALCAM in inflamed mucosa of IBD patients using qRT-PCR and immunohistochemistry. Phenotypic properties of CD6low/- and CD6highCD4+ T cells were determined by flow cytometry, qRT-PCR, and ELISA. ALCAM-Fc fusion protein was used to evaluate the role of CD6-ALCAM engagement in regulating IBD CD4+ T cell activation and proliferation.
Results: Expression of CD6 and its ligand ALCAM was markedly increased in inflamed mucosa of IBD patients compared with normal controls, and significantly correlated with disease activity indexes of IBD patients. Interestingly, CD6highCD4+ T cells of IBD patients exhibited significantly higher pathogenicity compared with CD6low/-CD4+ T cells, characterized by enhanced T cell activation and preferential Th1 and Th17 cell phenotypes, but markedly decreased proportion of nTreg [CD25highFoxp3+, CD25highCD127low] cells. Importantly, inclusion of ALCAM Fc fusion protein significantly facilitated IBD CD6highCD4+ T cells to proliferate and differentiate into Th1/Th17 cells compared with hIgG1 Fc-treated controls.
Conclusions: These data indicate that overexpression of CD6 and ALCAM in inflamed mucosa of IBD patients accelerates intestinal mucosal immune responses via promoting CD4+ T cell proliferation and differentiation into Th1/Th17 cells. Thus, CD6 may serve as a novel therapeutic target for treatment of IBD.
PMID: 30395204 [PubMed – as supplied by publisher]