Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan.
J Dermatol. 2019 Jan;46(1):37-42. doi: 10.1111/1346-8138.14696. Epub 2018 Nov 7.
The T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) is a co-inhibitory receptor mainly expressed on T cells. Although TIGIT plays an important role in various autoimmune diseases, its role in atopic dermatitis (AD) remains unclear. In this study, we examined the expression levels of TIGIT and their association with clinical features in patients with AD. TIGIT expression on CD4 T cells, central memory T cells, effector memory T cells and regulatory T cells was determined by flow cytometry. CD4 T cells exhibited enhanced TIGIT expression in patients with AD compared with healthy individuals. In particular, effector memory T cells and regulatory T cells, but not central memory T cells, exhibited higher TIGIT expression in patients with AD than in healthy individuals. The frequency of TIGIT cells among CD4 T cells was significantly increased in patients with mild AD compared with healthy individuals, while decreased in patients with severe AD. Consistently, the frequency of TIGIT cells among CD4 T cells was negatively correlated with both serum thymus and activation-regulated chemokine levels and immunoglobulin E levels in patients with AD. Furthermore, TIGIT expression on CD4 T cells inhibited cell proliferation in patients with AD. These results suggest that TIGIT expression on CD4 T cells in patients with AD may be increased to suppress chronic cutaneous inflammation. Moreover, TIGIT expression may be impaired in a subset of patients with AD, leading to a deterioration of skin inflammation. Our study may provide new insight into a TIGIT pathway-based therapeutic approach for AD.
T 细胞免疫球蛋白和免疫受体酪氨酸抑制基序结构域(TIGIT)是一种主要在 T 细胞上表达的共抑制受体。尽管 TIGIT 在各种自身免疫性疾病中发挥重要作用,但它在特应性皮炎(AD)中的作用尚不清楚。在这项研究中,我们检查了 TIGIT 的表达水平及其与 AD 患者临床特征的关联。通过流式细胞术测定 CD4 T 细胞、中央记忆 T 细胞、效应记忆 T 细胞和调节性 T 细胞上的 TIGIT 表达。与健康个体相比,AD 患者的 CD4 T 细胞表现出增强的 TIGIT 表达。特别是效应记忆 T 细胞和调节性 T 细胞,而不是中央记忆 T 细胞,在 AD 患者中比健康个体表达更高的 TIGIT。与健康个体相比,轻度 AD 患者中 CD4 T 细胞中 TIGIT 细胞的频率显著增加,而重度 AD 患者中则减少。一致地,AD 患者 CD4 T 细胞中 TIGIT 细胞的频率与血清胸腺和激活调节趋化因子水平和免疫球蛋白 E 水平呈负相关。此外,CD4 T 细胞上的 TIGIT 表达抑制了 AD 患者的细胞增殖。这些结果表明,AD 患者 CD4 T 细胞上的 TIGIT 表达可能增加以抑制慢性皮肤炎症。此外,AD 患者的亚群中可能存在 TIGIT 表达受损,导致皮肤炎症恶化。我们的研究可能为 AD 的 TIGIT 通路为基础的治疗方法提供新的见解。