Recovery of CD226-TIGIT+FoxP3+ and CD226-TIGIT-FoxP3+ regulatory T cells contributes to clinical remission from active stage in ulcerative colitis patients

Ulcerative colitis (UC) is a chronic inflammatory immune-related disease. Imbalance between pathogenic cells and immunosuppressive cells is associated with disease activity of UC. Regulatory T cells (Tregs) are critical for this immune homeostasis. However, the clinical significance of CD226 and TIGIT expressions on FoxP3+Tregs in UC remains unclear. Comprehensive analyses of CD226 and TIGIT expressions on FoxP3+Tregs were performed by flow cytometry in 72 UC patients and 35 healthy controls, and ten active UC patients achieving remission after treatment with 5-aminosalicylic acid were followed up. Expressions of β7, α4 and αE on FoxP3+Tregs were analyzed. Clinical indicators were retrospectively acquired and serum cytokines were detected using ELISA, and their correlations with FoxP3+Treg subsets were conducted. In active UC, levels of FoxP3+Tregs and CD226−FoxP3+Tregs regardless of TIGIT expression were significantly decreased while percentages of CD226+TIGIT−FoxP3+Tregs and CD226+TIGIT+FoxP3+Tregs were obviously increased. The expressions of β7, α4β7 and αEβ7 in FoxP3+Tregs, CD226−TIGIT+FoxP3+Tregs and CD226−TIGIT−FoxP3+Tregs were significantly elevated in active UC. Furthermore, inverse correlations were found between FoxP3+Tregs, CD226−TIGIT+FoxP3+Tregs, CD226−TIGIT−FoxP3+Tregs and serum CRP, as well as Mayo scores. IL-10 was reduced and positively correlated with CD226−TIGIT+FoxP3+Tregs and CD226−TIGIT−FoxP3+Tregs while IL-12 was increased and negatively correlated with CD226−TIGIT+FoxP3+Tregs and CD226−TIGIT−FoxP3+Tregs in active UC. In follow-up patients, the levels of FoxP3+Tregs, CD226−TIGIT+FoxP3+Tregs and CD226−TIGIT−FoxP3+Tregs and serum IL-10 levels were significantly recovered when achieving remission after treatment. Lack of CD226 expression on FoxP3+Tregs regardless of TIGIT expression may play an important role in exhibiting their suppressive function and preventing from disease activity in UC.