Decreased expression of TIGIT in NK cells correlates negatively with disease activity in systemic lupus erythematosus.

It is well-known that decreased levels of NK cells are found in patients with systemic lupus erythematosus (SLE). However, the mechanism of deregulation of NK cells in SLE is largely unknown. In this study, expression of T-cell immunoreceptor with Ig and immunoreceptor tyrosine-based inhibitory domains (TIGIT) on NK cells was determined by flow cytometry and correlation with markers of autoimmune response, inflammation, disease activity and severity of SLE was further analyzed. Moreover, the function of TIGIT on NK cells in SLE was investigated. We have found that the frequency of TIGIT-expressing NK cells was significantly decreased in SLE patients. The frequency of TIGIT-expressing NK cells in patients with SLE was decreased significantly in subjects with low complement, positive anti-ribosomal RNP (anti-rRNP), and high SLE Disease Activity Index (SLEDAI) score. Furthermore, the frequency of TIGIT-expressing NK cells was significantly increased in SLE patients after regular treatment. In addition, the activation marker CD69, degranulation marker CD107a and cytokine IFN-γ production potential of TIGIT+ NK cells were significantly lower than those of TIGIT- NK cells. Blocking the TIGIT pathway by functional anti-TIGIT monoclonal antibody restored IFN-γ secretion of NK cells. In conclusion, TIGIT expression was significantly decreased on NK cells in patients with SLE and correlated negatively with disease activity and severity of SLE. Additionally, the functional potential of TIGIT+ NK cells was significantly decreased compared with TIGIT- NK cells. This study reveals that TIGIT is a powerful negative regulator of NK cells in SLE. IJCEP