Fig. 5

Activated T cells suppress MDSC function through the JNK-NMDAR-ARG-1 pathway. a The levels of p-NF-κB, NF-κB, p-STAT1, STAT1, p-STAT3, STAT3, p-mTOR, mTOR, p-JNK, JNK, p-AKT, ATK, p-ERK, and ERK were examined using western blotting in MDSCs stimulated with ASN for 3 days. b–d MDSCs were treated with ASN and the STAT1 inhibitor Fludara (10 μg/mL), the NF-κB inhibitor Bay 11–7082 (5 μg/mL), the mTOR inhibitor rapamycin (5 μg/mL), the STAT3 inhibitor NSC 74859 (5 μg/mL), or JNK inhibitors (5 μg/mL) for 3 days. The expression of M-CSFR (b) and ARG-1 (c), and the suppressive capacity (d) of MDSCs were assessed. e–g MDSCs were left untreated or stimulated with the JNK agonist anisomycin (1 μg/mL) and the expression of M-CSFR (e) and ARG-1 (f) and the suppressive capacity (g) of MDSCs were measured. h The mRNA and protein levels of NMDAR in MDSCs were determined following exposure to ASN. i, j NMDAR expression on MDSCs in the presence of ASN combined with the indicated inhibitors (i) or the JNK agonist anisomycin (j) alone was examined using western blotting. k–m The phenotype and suppressive activity of MDSCs were determined after stimulation with ASN in the presence or absence of JNK inhibitors or the NMDAR inhibitor MK801 (50 μmol/L). Immunoblots are representative of 3 subjects (a, c, f, h, i, j, l). The data were generated from three independent experiments (b, d, e, h, k, m) or four independent experiments (g). The data are shown as the mean ± SEM. *p < 0.05; **p < 0.01