College of Forensic Medicine, Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Hebei Medical University, Shijiazhuang 050017, China.
Institute of Basic Medicine, Hebei Medical University, Shijiazhuang 050017, China.
Exp Biol Med (Maywood). 2023 Oct;248(20):1718-1731. doi: 10.1177/15353702231198083. Epub 2023 Oct 3.
Immune balance is crucial for an organism's survival and is inseparable from the regulation of the nervous system. Accumulating evidence indicates that cholecystokinin (CCK) plays an important role in mediating the immune response through the activation of cholecystokinin receptors (CCKRs). However, it remains unclear whether CCKRs deficiency may impair immune balance. Here, we showed that CCK2R-deficient adult mice were immunocompromised and had an increased risk of shock and even death in an endotoxemia (ETM)/endotoxin shock (ES) model. In addition, in both adult and juvenile mice, CCK2R deficiency not only influenced the development of CD4 single-positive (SP) thymocytes in thymic positive selection but also decreased the population of CD3 CD4 T cells in the spleen. More importantly, CCK2R deficiency inhibited the expression of major histocompatibility complex class II (MHC II) and CD83 on cortical thymic epithelial cells (cTECs) in juvenile and adult mice. Overall, our study suggests that CCK2R is essential for maintaining CD4 T cell development in the thymus and reveals that CCK2R plays an important role in maintaining immune balance.
免疫平衡对于生物体的生存至关重要，而它与神经系统的调节密不可分。越来越多的证据表明，胆囊收缩素（Cholecystokinin，CCK）通过激活胆囊收缩素受体（Cholecystokinin Receptors，CCKRs）在介导免疫反应中发挥重要作用。然而，CCKRs 缺乏是否会损害免疫平衡仍不清楚。在这里，我们发现 CCK2R 缺失的成年小鼠在脂多糖（Endotoxin，ETM）/内毒素休克（Endotoxin Shock，ES）模型中免疫功能受损，休克甚至死亡的风险增加。此外，在成年和幼年小鼠中，CCK2R 缺失不仅影响胸腺阳性选择中 CD4 单阳性（Single-Positive，SP）胸腺细胞的发育，还降低了脾脏中 CD3 CD4 T 细胞的数量。更重要的是，CCK2R 缺失抑制了幼年和成年小鼠皮质胸腺上皮细胞（Cortical Thymic Epithelial Cells，cTECs）上主要组织相容性复合体 II（MHC II）和 CD83 的表达。总的来说，我们的研究表明 CCK2R 对于维持胸腺中 CD4 T 细胞的发育是必不可少的，并揭示了 CCK2R 在维持免疫平衡方面的重要作用。
