Exploration of the relationship between hippocampus and immune system in schizophrenia based on immune infiltration analysis.
Exploration of the relationship between hippocampus and immune system in schizophrenia based on immune infiltration analysis.
复制标题
DOI：
10.3389/fimmu.2022.878997
复制
发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
免疫功能障碍与精神分裂症（SZ）的发病机制有关。尽管先前的研究显示免疫失调与SZ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，旨在从脑区、免疫细胞、基因和通路等方面更详细地探讨精神分裂症与免疫系统之间的关系。在这里，我们综合分析了SZ组和对照组的海马体（HPC）、前额叶皮质（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中存在20个免疫相关基因（IRGs）和42个免疫通路。免疫浸润分析结果显示，HPC的差异免疫细胞为效应记忆T （Tem）细胞。免疫相关DEGs （IDEGs）与免疫细胞的相关性进一步分析显示，NPY、BLNK、OXTR和FGF12与Tem细胞有中度相关性。功能通路分析表明，这4个基因可能通过调控PI3K-AKT通路和神经活性配体-受体相互作用通路影响Tem。受试者工作特征曲线（ROC）分析结果显示，这4个基因具有较高的诊断能力（AUC=95.19%）。最后成功复制疾病动物模型，并利用real-time PCR和western blot进一步验证。这些结果表明这些基因表达变化与我们之前的表达谱一致。综上所述，我们的研究结果表明，SZ的HPC可能与免疫紊乱更密切相关，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，Immucell AI工具首次应用于SZ的免疫浸润分析，有助于从新的角度更好地理解免疫功能障碍在SZ中的作用。
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 NPY, BLNK, OXTR, and FGF12, 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.
影响因子：
6.8
作者：
Polushina T;Giddaluru S;Bettella F;Espeseth T;Lundervold AJ;Djurovic S;Cichon S;Hoffmann P;Nöthen MM;Steen VM;Andreassen OA;Le Hellard S
通讯作者：
Le Hellard S