Rapamycin reduces effector/memory T cell response in mouse model of steroid-resistant asthma

In a study on patients with allergic asthma, it was reported that effector/memory Th2 cells are also related to steroid responsiveness. We examined changes in effector/memory T cell response by rapamycin administration in particulate matter-induced steroid-resistant asthma mouse model established by our research team. After the resolution period, the recall response to the allergen was examined, and experiments were conducted with in vitro experiments and PBMCs from the steroid Non-Responder group. When Dp was administered one day before analysis after the resolution period, airway hyperresponsiveness, Dp-specific IgG1 in serum, eosinophils, neutrophils, and inflammation, the expression of IL-13+pmtor+ or IL-17+pmtor+ in CD44 high CD62L low cell population in lung tissue were all significantly increased in the Dp/PM+Dp administration group, and on the contrary, Dp/PM/Rapa+Dp treatment groups all showed a significant decrease. When CD4 T cells isolated from mice administered Dp/PM were treated with Rapamycin, the IL-13+p-mTOR+, IL-17+p-mTOR+, and IL-5+p-mTOR+ populations were significantly decreased. Additionally, when these Rapamycin-treated CD4 T cells were co-cultured with PM/Dp-stimulated BMDCs, the same results were obtained. In human PBMC, In the steroid Non-Responder (NR) group, cytokines with p-mTOR double-positive population of effector/memory CD4 T cells (CCR7-CD45RA-CD4+ in CD62-CD27-CD45RO+) was significantly higher than that of the Normal or steroid Responder (R) groups. Through mouse experiments and human studies, it was confirmed that effector/memory CD4 T cells are thought to be important in steroid resistance and can be reduced by rapamycin.