Objective This study aimed to explore the mechanism of exosome secreted by bone mesenchy⁃ mal stem cells overexpressing IDO（BMSCIDO⁃exosome）inhibiting the activation of T and DC cells. Method The experimental group consisted of BMSCIDO⁃exosome was co⁃cultured with DC and T cells. In co⁃cultured DC and T cells，the expression of miR⁃540⁃3p，CD74，CD28，CCL4，p⁃ERK1/2，p⁃NF⁃κB，and p⁃AKT was detected. The targeted binding of miRNA⁃540⁃3p to CD74 gene was also verified. Results In the experimental group，miR⁃540⁃ 3p expression increased in DC cells while CD74 and p⁃p65 expression decreased. MiR⁃540⁃3p expression increased in T cells，while CD74 and p⁃AKT expression decreased. MiRNA⁃540⁃3p has been shown to bind specifically to CD74. Conclusions BMSCIDO⁃exosome could inhibit the activation of DC and T cells through the miRNA⁃540⁃3p （+）/CD74（-）/p⁃NF⁃κB molecular axis and the miRNA⁃540⁃3p（+）/CD74（-）/p⁃AKT（-）molecular axis，respec⁃ tively.