CCK2-receptor deficiency impairs immune balance by influencing CD4 + T cells development by inhibiting cortical-thymic-epithelial-cells

Abstract

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.