Co-inhibitory pathways have a fundamental function in regulating T cell responses and control the balance between promoting efficient effector functions and restricting immune pathology. The TIGIT pathway has been implicated in promoting T cell dysfunction in chronic viral infection. Importantly, TIGIT signaling is functionally linked to IL-10 expression, which has an effect on both virus control and maintenance of tissue homeostasis. However, whether TIGIT has a function in viral persistence or limiting tissue pathology is unclear. Here we report that TIGIT modulation effectively alters the phenotype and cytokine profile of T cells during influenza and chronic LCMV infection, but does not affect virus control in vivo. Instead, TIGIT has an important effect in limiting immune pathology in peripheral organs by inducing IL-10. Our data therefore identify a function of TIGIT in limiting immune pathology that is independent of viral clearance.

共抑制途径在调节 T 细胞反应和控制促进有效效应功能和限制免疫病理之间的平衡方面具有基本功能。 TIGIT 通路与促进慢性病毒感染中的 T 细胞功能障碍有关。重要的是，TIGIT 信号传导在功能上与 IL-10 表达相关，IL-10 对病毒控制和组织稳态的维持都有影响。然而，TIGIT 是否在病毒持久性或限制组织病理学方面具有功能尚不清楚。在这里，我们报告 TIGIT 调节有效地改变了流感和慢性 LCMV 感染期间 T 细胞的表型和细胞因子谱，但不影响体内病毒控制。相反，TIGIT 通过诱导 IL-10 在限制外周器官的免疫病理方面具有重要作用。因此，我们的数据确定了 TIGIT 在限制免疫病理学方面的功能，该功能独立于病毒清除。