Objective To investigate the roles of glutamate signaling pathway in the activation of human peripheral blood lymphocytes(PBLs) and pathogenesis of vitiligo.Methods Peripheral blood lymphocytes (PBLs) isolated from 5 patients with generalized vitiligo and 5 healthy controls were cultured in vitro.Flow cytometry was performed to quantify the expression of CD25 and interferon-γ on PBLs derived from healthy controls and treated with MK801 (a non-competitive antagonist of N-methyl-D-aspartic acid receptor,NMDAR) at 100 μmol/L or phosphate buffered saline (PBS) for 48 hours,as well as the level of reactive oxygen species (ROS) in the controlderived PBLs treated with MK801 at 100 μmol/L,NMDA (an agonist of N-methyl-D-aspartic acid receptor) at 0.5 mmol/L or PBS for 48 hours.The protein and mRNA expressions of NMDAR1 and NMDAR2A were measured by flow cytometry and real-time PCR,respectively,in PBLs from the healthy controls and vitiligo patients.Immunohistochemistry was used to observe the expressions of NMDAR1 and NMDAR2A in tissue specimens from depigmented and postinflammatory hyperpigmentation lesions of the patients with vitiligo and from normal skin of the healthy controls.Results Compared with the PBS-treated PBLs from the healthy controls,the MK801-treated PBLs showed a downregulated expression of CD25 (7.28％ ± 0.18％ vs.16.02％ ± 0.42％,P ＜ 0.01),but an upregulated proportion of CD25+IFN-γ+ lymphocytes (1.79％ ± 0.09％ vs.0.78％ ± 0.06％,P ＜ 0.01),and the NMDA-treated PBLs displayed a higher ROS level (101.1 ± 3.50 vs.69.80 ± 2.08,P＜ 0.01 ).The protein expression of NMDAR1 in PBLs was significantly higher in vitiligo patients than in the healthy controls (3.85 ± 2.17 vs.0.97 ±0.55,P ＜ 0.05).Conclusion Glutamate signaling pathway may be involved in the immunopathogenesis of vitiligo via affecting the secretion of interferon-γ by,and ROS level in,activated lymphocytes.