The TIGIT Signaling Pathway Negatively Regulates CD4+ T Cells In Systemic Lupus Erythematosus

Objective.The mechanism of the downregulation of CD4+ T cells in SLE is still largely unknown.T-cell immunoglobulin and ITIM domain(TIGIT)is a new inhibitory receptor expressed on activated CD4+ T cells.Here,we addressed the role of TIGIT in the pathogenesis of SLE.Methods.The phenotype and function of TIGIT-expressed CD4+ T cells were examined in healthy individuals and SLE patients by flow cytometry.The effect of activation TIGIT pathway on CD4+ T cells or on the development of MRL/lpr mice was assessed.Results.The expression of TIGIT was significantly elevated on CD4+ T cells in SLE patients and highly correlated with the activity of the disease.TIGIT+ CD4+ T cells had a more activated phenotype than TIGIT-CD4+ T cells in both SLE patients and healthy individuals.Reversely,after stimulation,the activation,proliferation and cytokine production of TIGIT-CD4+ T cells were significantly higher than TIGIT+ CD4+ T cells.Furthermore,using of CD155 protein to activate TIGIT pathway could decrease the activation,proliferation and cytokine production of CD4+ T cells from SLE patients or healthy individuals,and administration of which in vivo resulted in a delayed development of SLE in mice.Conclusion.These observations suggest that the TIIGT signalling pathway negatively regulate CD4+ T cells in SLE,which might be used as a prominent therapeutic target for this disease.