TIGIT signalling pathway negatively regulates CD 4 + T‐cell responses in systemic lupus erythematosus

Summary B‐lymphocyte hyperactivity in systemic lupus erythematosus ( SLE ) is T‐cell‐dependent, and CD 4 + T‐cell activation is essential to SLE pathogenesis. However, the mechanism of the deregulation of CD 4 + T cells in SLE is largely unknown. T‐cell immunoglobulin and ITIM domain ( TIGIT ) is a new inhibitory receptor preferentially expressed on activated CD 4 + T cells. Here, we address the role of TIGIT in the pathogenesis of SLE . Our results showed that TIGIT expression on CD 4 + T cells was significantly elevated in patients with SLE and highly correlated with the activity of the disease. TIGIT + CD 4 + T cells from both healthy individuals and patients with SLE had a more activated phenotype than TIGIT − CD 4 + T cells. In contrast, the activation, proliferation and cytokine production potential of TIGIT + CD 4 + T cells were significantly lower than those of TIGIT − CD 4 + T cells. Furthermore, activation of the TIGIT pathway by using CD 155 could substantially down‐regulate the activities of CD 4 + T cells from SLE patients in vitro , and in vivo administration of CD 155 resulted in a delayed development of SLE in MRL /lpr mice. TIGIT is a powerful negative regulator of CD 4 + T cells in SLE , which suggests that the TIGIT signalling pathway may be used as a potential therapeutic target for treating this disease.