Bacillus Calmette-Guerin-induced interleukin-10 inhibits S100A8/A9 production and hinders development of T helper type 1 memory in mice
Bacillus Calmette-Guerin-induced interleukin-10 inhibits S100A8/A9 production and hinders development of T helper type 1 memory in mice
复制标题
DOI：
10.1002/eji.202250204
复制
发表时间：
2023-02-16
影响因子：
5.4
通讯作者：
Pan，Qin
中科院分区：
文献类型：
--
作者：
Wang，Yaping;Sun，Yuehua;Pan，Qin
由结核分枝杆菌引起的结核病是世界上人类死亡的主要原因之一。卡介苗在青少年和成人中提供有限的保护。为了探讨降低卡介苗疗效的因素，我们评估了白细胞介素（IL）‐10和警报因子S100A8/A9对T细胞记忆的影响。我们发现卡介苗诱导的IL - 10抑制了人外周血单核细胞和小鼠脾细胞中S100A8/A9的产生。在卡介苗免疫早期，S100A9缺乏抑制CD4+T细胞产生IFN - γ，阻碍效应记忆T辅助型1 （Th1）细胞的发展，而IL - 10缺乏促进Th1记忆，阻断IL - 10信号传导，增强Th1对m .tb的保护性回忆反应。IL‐10抑制转录因子CCAAT增强子结合蛋白β toS100a8/ A9启动子的结合，导致S100A8/A9减少。S100A8/A9异源二聚体通过CD4+T细胞晚期糖基化终产物信号受体增强IFN - γ的产生。我们的研究结果揭示了卡介苗免疫后Th1记忆的发展障碍，并阐明了IL - 10和S100A8/A9调控Th1记忆的机制。
Tuberculosis caused byMycobacterium tuberculosis (M.tb)is one of the main causes of human death in the world. Bacillus Calmette‐Guérin (BCG) provides limited protection in adolescents and adults. To explore the factors reducing efficacy of BCG vaccine, we assess the impacts of interleukin (IL)‐10 and alarmins S100A8/A9 on T‐cell memory. We found that BCG‐induced IL‐10 inhibited production of S100A8/A9 in human peripheral blood mononuclear cells (PBMCs) and murine splenocytes. S100A9 deficiency inhibited IFN‐γ production by CD4+T cells in the early phase of BCG immunization and hindered the development of effector memory T helper type 1 (Th1) cells, while IL‐10 deficiency promoted Th1 memory and blocking IL‐10 signaling enhanced Th1 protective recall response againstM.tb. IL‐10 inhibited the binding of transcription factor CCAAT enhancer binding protein beta toS100a8/a9promoter leading to S100A8/A9 reduction. S100A8/A9 heterodimer enhanced the IFN‐γ production via receptor for advanced glycation end products signaling in CD4+T cells. Our results demonstrate a hurdle to development of Th1 memory after BCG immunization and clarify the mechanism of the regulation of Th1 memory by IL‐10 and S100A8/A9.