Department of Clinical Laboratory, Peking University People's Hospital, Beijing, China.
Medical School of Chinese PLA & Department of Clinical Laboratory Medicine, Chinese People's Liberation Army General Hospital, Beijing, China.
Immunol Lett. 2020 Feb;218:30-39. doi: 10.1016/j.imlet.2019.12.007. Epub 2019 Dec 26.
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 FoxP3Tregs in UC remains unclear.
Comprehensive analyses of CD226 and TIGIT expressions on FoxP3Tregs 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 FoxP3Tregs were analyzed. Clinical indicators were retrospectively acquired and serum cytokines were detected using ELISA, and their correlations with FoxP3Treg subsets were conducted.
In active UC, levels of FoxP3Tregs and CD226FoxP3Tregs regardless of TIGIT expression were significantly decreased while percentages of CD226TIGITFoxP3Tregs and CD226TIGITFoxP3Tregs were obviously increased. The expressions of β7, α4β7 and αEβ7 in FoxP3Tregs, CD226TIGITFoxP3Tregs and CD226TIGITFoxP3Tregs were significantly elevated in active UC. Furthermore, inverse correlations were found between FoxP3Tregs, CD226TIGITFoxP3Tregs, CD226TIGITFoxP3Tregs and serum CRP, as well as Mayo scores. IL-10 was reduced and positively correlated with CD226TIGITFoxP3Tregs and CD226TIGITFoxP3Tregs while IL-12 was increased and negatively correlated with CD226TIGITFoxP3Tregs and CD226TIGITFoxP3Tregs in active UC. In follow-up patients, the levels of FoxP3Tregs, CD226TIGITFoxP3Tregs and CD226TIGITFoxP3Tregs and serum IL-10 levels were significantly recovered when achieving remission after treatment.
Lack of CD226 expression on FoxP3Tregs regardless of TIGIT expression may play an important role in exhibiting their suppressive function and preventing from disease activity in UC.
溃疡性结肠炎（UC）是一种慢性炎症性免疫相关疾病。致病性细胞与免疫抑制性细胞之间的失衡与 UC 的疾病活动有关。调节性 T 细胞（Tregs）对于这种免疫稳态至关重要。然而，CD226 和 TIGIT 在 UC 中的 FoxP3Tregs 表达的临床意义仍不清楚。
通过流式细胞术对 72 例 UC 患者和 35 例健康对照者的 FoxP3Tregs 上的 CD226 和 TIGIT 表达进行综合分析，并对 10 例接受 5-氨基水杨酸治疗后缓解的活动期 UC 患者进行随访。分析 FoxP3Tregs 上的β7、α4 和 αE 的表达。回顾性采集临床指标，采用 ELISA 检测血清细胞因子，并分析其与 FoxP3Treg 亚群的相关性。
在活动期 UC 中，无论 TIGIT 表达如何，FoxP3Tregs 和 CD226FoxP3Tregs 的水平均显著降低，而 CD226TIGITFoxP3Tregs 和 CD226TIGITFoxP3Tregs 的比例明显增加。FoxP3Tregs、CD226TIGITFoxP3Tregs 和 CD226TIGITFoxP3Tregs 上的β7、α4β7 和 αEβ7 表达均显著升高。此外，FoxP3Tregs、CD226TIGITFoxP3Tregs、CD226TIGITFoxP3Tregs 与血清 CRP 和 Mayo 评分呈负相关。IL-10 降低且与 CD226TIGITFoxP3Tregs 和 CD226TIGITFoxP3Tregs 呈正相关，而 IL-12 增加且与 CD226TIGITFoxP3Tregs 和 CD226TIGITFoxP3Tregs 呈负相关。在随访患者中，治疗后达到缓解时，FoxP3Tregs、CD226TIGITFoxP3Tregs 和 CD226TIGITFoxP3Tregs 的水平和血清 IL-10 水平均显著恢复。
无论 TIGIT 表达如何，FoxP3Tregs 上缺乏 CD226 表达可能在发挥其抑制功能和防止 UC 疾病活动方面发挥重要作用。
