Department of Psychiatry, First Hospital/First Clinical Medical College of Shanxi Medical University, Taiyuan, China.
Shanxi Key Laboratory of Artificial Intelligence Assisted Diagnosis and Treatment for Mental Disorder, First Hospital of Shanxi Medical University, Taiyuan, China.
Front Immunol. 2022 Aug 2;13:878997. doi: 10.3389/fimmu.2022.878997. eCollection 2022.
Immune dysfunction has been implicated in the pathogenesis of schizophrenia (SZ). Despite previous studies showing a broad link between immune dysregulation and the central nervous system of SZ, the exact relationship has not been completely elucidated. With immune infiltration analysis as an entry point, this study aimed to explore the relationship between schizophrenia and the immune system in more detail from brain regions, immune cells, genes, and pathways. Here, we comprehensively analyzed the hippocampus (HPC), prefrontal cortex (PFC), and striatum (STR) between SZ and control groups. Differentially expressed genes (DEGs) and functional enrichment analysis showed that three brain regions were closely related to the immune system. Compared with PFC and STR, there were 20 immune-related genes (IRGs) and 42 immune pathways in HPC. The results of immune infiltration analysis showed that the differential immune cells in HPC were effector memory T (Tem) cells. The correlation of immune-related DEGs (IDEGs) and immune cells further analysis showed that , , , and , were moderately correlated with Tem cells. Functional pathway analysis indicated that these four genes might affect Tem by regulating the PI3K-AKT pathway and the neuroactive ligand-receptor interaction pathway. The receiver operating characteristic curve (ROC) analysis results indicated that these four genes had a high diagnostic ability (AUC=95.19%). Finally, the disease animal model was successfully replicated, and further validation was conducted using the real-time PCR and the western blot. These results showed that these gene expression changes were consistent with our previous expression profiling. In conclusion, our findings suggested that HPC in SZ may be more closely related to immune disorders and modulate immune function through Tem, PI3K-Akt pathway, and neuroactive ligand-binding receptor interactions. To the best of our knowledge, the Immucell AI tool has been applied for the first time to analyze immune infiltration in SZ, contributing to a better understanding of the role of immune dysfunction in SZ from a new perspective.
免疫功能障碍与精神分裂症（SZ）的发病机制有关。尽管先前的研究表明免疫失调与 SZ 的中枢神经系统之间存在广泛的联系，但确切的关系尚未完全阐明。本研究以免疫浸润分析为切入点，旨在更详细地探讨 SZ 与免疫系统之间的关系，包括脑区、免疫细胞、基因和通路。在这里，我们全面分析了 SZ 组和对照组的海马体（HPC）、前额叶皮层（PFC）和纹状体（STR）。差异表达基因（DEGs）和功能富集分析表明，三个脑区与免疫系统密切相关。与 PFC 和 STR 相比，HPC 中有 20 个免疫相关基因（IRGs）和 42 个免疫途径。免疫浸润分析结果表明，HPC 中的差异免疫细胞是效应记忆 T（Tem）细胞。免疫相关 DEGs（IDEGs）与免疫细胞的相关性进一步分析表明，、、、和与 Tem 细胞中度相关。功能通路分析表明，这四个基因可能通过调节 PI3K-AKT 通路和神经活性配体-受体相互作用通路来影响 Tem 细胞。受试者工作特征曲线（ROC）分析结果表明，这四个基因具有较高的诊断能力（AUC=95.19%）。最后，成功复制了疾病动物模型，并使用实时 PCR 和 Western blot 进行了进一步验证。这些结果表明，这些基因表达的变化与我们之前的表达谱一致。总之，我们的研究结果表明，SZ 中的 HPC 可能与免疫紊乱更为密切相关，并通过 Tem、PI3K-Akt 通路和神经活性配体结合受体相互作用调节免疫功能。据我们所知，这是首次应用 Immucell AI 工具分析 SZ 中的免疫浸润，为从新的角度更好地理解免疫功能障碍在 SZ 中的作用提供了帮助。
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