CaMK4 promotes abortion-related Th17 cell imbalance by activating AKT/mTOR signaling pathway
CaMK4 promotes abortion-related Th17 cell imbalance by activating AKT/mTOR signaling pathway
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CaMK4通过激活AKT/mTOR信号通路促进流产相关Th17细胞失衡
DOI：
10.1111/aji.13315
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发表时间：
2020
影响因子：
3.6
通讯作者：
Yang Jing
中科院分区：
文献类型：
--
作者：
Chang Shuo;Yin Tailang;He Fan;Ding Jinli;Shang Ye;Yang Jing
问题沿着母胎界面的免疫微环境平衡与妊娠结局密切相关，过度的炎症反应会导致流产等病理性妊娠结局的发生。已有报道CaMK 4通过调节Th 17细胞在自身免疫性疾病中发挥重要作用。然而，CaMK 4是否与自然流产或沿沿着母胎界面的免疫微环境有关仍不清楚。研究方法本研究中，我们建立了正常妊娠和LPS诱导的小鼠流产模型，并给予CaMK 4抑制剂KN-93，以研究免疫反应的变化和机制。在子宫胎盘复合体和脾脏中评估CaMK 4的表达。此外，Th 17细胞的浸润和功能进行了估计在外周组织和子宫胎盘complex.ResultsThe表达CaMK 4在子宫胎盘复合体和脾脏中的LPS治疗组显着高于在正常妊娠组。KN-93，CaMK 4抑制剂，逆转胎儿吸收和过度炎症。详细地说，KN-93导致Th 17细胞向外周组织和子宫胎盘复合体的浸润减少，Th 17细胞的功能受到抑制。结论CaMK 4是通过AKT/mTOR信号通路促进Th 17细胞增殖并增强其功能的重要调节因子。抑制CaMK 4可以逆转沿着母胎界面的免疫失衡，改善妊娠结局。
ProblemThe balance of the immune microenvironment along the maternal‐fetal interface is closely related to pregnancy outcomes, with excessive inflammatory reactions leading to the occurrence of pathological pregnancy outcomes such as abortion. CaMK4 has been reported to play a significant role in autoimmune diseases through the regulation of Th17 cells. However, whether CaMK4 is associated with spontaneous abortion or the immune microenvironment along the maternal‐fetal interface remains unclear.Methods of studyIn this study, we constructed normal pregnancy and LPS‐induced abortion models in mice, and a CaMK4 inhibitor called KN‐93 was administered to investigate the changes in and mechanisms of the immune response. The expression of CaMK4 was evaluated in the uteroplacental complex and spleen. Furthermore, the infiltration and function of Th17 cells were estimated in peripheral tissues and the uteroplacental complex.ResultsThe expression of CaMK4 in the uteroplacental complex and spleen was significantly higher in the LPS‐treated group than in the normal pregnancy group. KN‐93, the CaMK4 inhibitor, reversed fetal resorption and excessive inflammation. In detail, KN‐93 led to reduced infiltration of Th17 cells into peripheral tissues and the uteroplacental complex, and the functions of Th17 cells were inhibited. In addition, CaMK4 promoted the AKT/mTOR signaling pathway, which is one of the mechanisms that regulate the immune microenvironment.ConclusionCaMK4 is a critical regulator that promotes the expansion of Th17 cells and enhances their functions through the AKT/mTOR signaling pathway. The inhibition of CaMK4 can reverse the immune imbalance along the maternal‐fetal interface and improve pregnancy outcomes.