接头蛋白RACK1在调节性B细胞中的表达对应激相关神经炎症的调控作用与机制

我国正处于快速发展的转型期，应激相关精神心理障碍特别是抑郁症的发病率不断升高，但临床上还缺乏有效干预手段。我们和同行的工作揭示：长期应激状态下，外周炎性特征增强而免疫调节能力下降，推动神经炎症发生发展、继而加重负面情绪。因此，增强免疫调节成为干预新策略，但应激损伤和免疫调节细胞的交互作用机制不清楚。我们长期从事接头蛋白RACK1的体内功能研究，最近发现应激状态B细胞中RACK1的缺失并不影响B细胞数量，但可逆转IL-10+ Bregs比例的降低和小鼠行为学缺陷。基于依托单位在应激、认知方面完善的技术平台和资源优势，我们拟探讨应激损伤与神经炎症的动态关联规律；应激对不同亚群Bregs的影响与机制；RACK1对不同亚群Bregs的影响与机制；RACK1缺失的 Bregs与应激相关神经炎症的交互作用与机制。工作的完成可推进应激相关精神心理障碍病因学研究、为动态监测提供标志物、为干预治疗提供新靶点

With China's rapid development, people in China are facing more and more stress-related mood disorders, especially major depression, but the clinical intervention is lacking. We and other colleagues have disclosed that persistent stress leads to enhanced systemic inflammation and impaired immunoregulation, which promotes the onset and progression of neuroinflammation and thereby worsens negative mood. Therefore, it has been proposed that enhancing immunoregulation might be helpful. However, it remains elusive how stress might impact regulatory immune cells and vice versa. We have been long involved in the in vivo function of adaptor RACK1. Recently, we have found B cell-specific RACK1 deficiency does not affect the number of B cells after the mice undergo restraint stress. But the mice with B cell-specific RACK1 deficiency show more IL-10+ Bregs and alleviated behavior defects. Based on the resources of our facility on the study of stress and cognition, we prepare to investigate the location and cellular characteristics of stress-triggered neuroinflammation; how stress or RACK1 might affect different subsets of Bregs and the underlying mechanisms; and how RACK1-deficient Bregs and stress-triggered neuroinflammation might impact each other and the underlying mechanisms. The corresponding findings might achieve therorical breakthroughs about the pathogenic mechanisms of stress-related mood disorders, provide monitoring marker(s), and provide new intervention tas).