The alteration of IL-17 signaling pathway in bipolar disorder: a preliminary study with transcriptomic perspective
ObjectiveBipolar Disorder (BD) is a complex psychiatric condition influenced by genetic and environmental factors. This study aims to explore global mRNA expression in Peripheral blood white cells (PBMC) of BD patients.MethodsWe analyzed whole-genome gene expression profiles from PBMC of 12 BD state...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-06-01
|
| Series: | Frontiers in Psychiatry |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fpsyt.2025.1539038/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849734169774522368 |
|---|---|
| author | Xiaobo Wang Xiaobo Wang Su Yu Zhen Gao Fangming Xu Yumei Wang Yumei Wang Yumei Wang Tianle Zhang Tingting Xie Xihua Jia |
| author_facet | Xiaobo Wang Xiaobo Wang Su Yu Zhen Gao Fangming Xu Yumei Wang Yumei Wang Yumei Wang Tianle Zhang Tingting Xie Xihua Jia |
| author_sort | Xiaobo Wang |
| collection | DOAJ |
| description | ObjectiveBipolar Disorder (BD) is a complex psychiatric condition influenced by genetic and environmental factors. This study aims to explore global mRNA expression in Peripheral blood white cells (PBMC) of BD patients.MethodsWe analyzed whole-genome gene expression profiles from PBMC of 12 BD states-manic (BD-M), 12 BD states-depressive (BD-D), and 12 matched healthy controls (HC) using microarrays. Validation of differentially expressed genes within the IL-17 pathway was conducted through qRT-PCR, while ELISA measured specific protein levels. GO and KEGG pathway enrichment analyses were performed, alongside PPI analysis and Gene Set Variation Analysis (GSVA) to assess immune cell infiltration.ResultsIn the comparison between BD and HC, a total of 304 differentially expressed genes (DEGs) were identified, of which 217 genes were upregulated and 87 genes were downregulated. In the comparisons between BD and HC, BD-M and HC, and BD-D and HC, 91 DEGs were found. Enrichment analysis suggested that biological processes and signaling pathways related to extracellular matrix, stress response, heparin binding, and immune inflammation were upregulated in the BD group. KEGG analysis and PPI results indicate that the IL-17 signaling pathway plays an important role in BD and its subtypes. In the IL-17 signaling pathway, compared to HC, the expression of Jun, Fosb, Fosl1, TNFAIP3, NFKBIA, CXCL2, CXCL8, IL6 and IL17 genes was upregulated in BD patients. RT-qPCR analysis showed that the expression of Jun, Fosb, Fosl1, NFKBIA, TNFAIP3, CXCL2, and CXCL8 genes was significantly upregulated in BD, ELISA results indicated that the protein levels of CXCL8/IL-8, IL-6 and IL-17 in the BD group were significantly higher than those in the HC group (all P < 0.05). Immune infiltration analysis showed that central memory CD4+ T cells (P=0.010), eosinophils (P=0.038), and mast cells (P=0.029) were increased in infiltration in the BD group.ConclusionThis study integrates transcriptomics and immune microenvironment analysis, suggesting that the IL-17 signaling pathway may be involved in the pathogenesis of BD and its subtypes through inflammation triggered by chemokines. This research deepens our understanding of the molecular mechanisms of BD and emphasizes the importance of the immune system in its pathology. |
| format | Article |
| id | doaj-art-ed3b391706344b0fb9847e95e79f3ce2 |
| institution | DOAJ |
| issn | 1664-0640 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Psychiatry |
| spelling | doaj-art-ed3b391706344b0fb9847e95e79f3ce22025-08-20T03:07:51ZengFrontiers Media S.A.Frontiers in Psychiatry1664-06402025-06-011610.3389/fpsyt.2025.15390381539038The alteration of IL-17 signaling pathway in bipolar disorder: a preliminary study with transcriptomic perspectiveXiaobo Wang0Xiaobo Wang1Su Yu2Zhen Gao3Fangming Xu4Yumei Wang5Yumei Wang6Yumei Wang7Tianle Zhang8Tingting Xie9Xihua Jia10Department of Psychiatry, the First Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Clinical Psychology, The First Central Hospital of Baoding, Baoding, Hebei, ChinaDepartment of Psychiatry, the First Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaInstitute of Brain Science and Brain-Inspired Research, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shangdong, ChinaDepartment of Psychiatry, the First Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Psychiatry, the First Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaInstitute of Brain Science and Brain-Inspired Research, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shangdong, ChinaDepartmentof Psychology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shangdong, ChinaDepartment of Psychiatry, the First Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaInstitute of Brain Science and Brain-Inspired Research, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shangdong, ChinaDepartment of Oncology, The First Central Hospital of Baoding, Baoding, Hebei, ChinaObjectiveBipolar Disorder (BD) is a complex psychiatric condition influenced by genetic and environmental factors. This study aims to explore global mRNA expression in Peripheral blood white cells (PBMC) of BD patients.MethodsWe analyzed whole-genome gene expression profiles from PBMC of 12 BD states-manic (BD-M), 12 BD states-depressive (BD-D), and 12 matched healthy controls (HC) using microarrays. Validation of differentially expressed genes within the IL-17 pathway was conducted through qRT-PCR, while ELISA measured specific protein levels. GO and KEGG pathway enrichment analyses were performed, alongside PPI analysis and Gene Set Variation Analysis (GSVA) to assess immune cell infiltration.ResultsIn the comparison between BD and HC, a total of 304 differentially expressed genes (DEGs) were identified, of which 217 genes were upregulated and 87 genes were downregulated. In the comparisons between BD and HC, BD-M and HC, and BD-D and HC, 91 DEGs were found. Enrichment analysis suggested that biological processes and signaling pathways related to extracellular matrix, stress response, heparin binding, and immune inflammation were upregulated in the BD group. KEGG analysis and PPI results indicate that the IL-17 signaling pathway plays an important role in BD and its subtypes. In the IL-17 signaling pathway, compared to HC, the expression of Jun, Fosb, Fosl1, TNFAIP3, NFKBIA, CXCL2, CXCL8, IL6 and IL17 genes was upregulated in BD patients. RT-qPCR analysis showed that the expression of Jun, Fosb, Fosl1, NFKBIA, TNFAIP3, CXCL2, and CXCL8 genes was significantly upregulated in BD, ELISA results indicated that the protein levels of CXCL8/IL-8, IL-6 and IL-17 in the BD group were significantly higher than those in the HC group (all P < 0.05). Immune infiltration analysis showed that central memory CD4+ T cells (P=0.010), eosinophils (P=0.038), and mast cells (P=0.029) were increased in infiltration in the BD group.ConclusionThis study integrates transcriptomics and immune microenvironment analysis, suggesting that the IL-17 signaling pathway may be involved in the pathogenesis of BD and its subtypes through inflammation triggered by chemokines. This research deepens our understanding of the molecular mechanisms of BD and emphasizes the importance of the immune system in its pathology.https://www.frontiersin.org/articles/10.3389/fpsyt.2025.1539038/fullbipolar disorderDEGs (differentially expressed genes)IL-17 pathwayimmunoinflammatory responseimmune infiltration analysis |
| spellingShingle | Xiaobo Wang Xiaobo Wang Su Yu Zhen Gao Fangming Xu Yumei Wang Yumei Wang Yumei Wang Tianle Zhang Tingting Xie Xihua Jia The alteration of IL-17 signaling pathway in bipolar disorder: a preliminary study with transcriptomic perspective Frontiers in Psychiatry bipolar disorder DEGs (differentially expressed genes) IL-17 pathway immunoinflammatory response immune infiltration analysis |
| title | The alteration of IL-17 signaling pathway in bipolar disorder: a preliminary study with transcriptomic perspective |
| title_full | The alteration of IL-17 signaling pathway in bipolar disorder: a preliminary study with transcriptomic perspective |
| title_fullStr | The alteration of IL-17 signaling pathway in bipolar disorder: a preliminary study with transcriptomic perspective |
| title_full_unstemmed | The alteration of IL-17 signaling pathway in bipolar disorder: a preliminary study with transcriptomic perspective |
| title_short | The alteration of IL-17 signaling pathway in bipolar disorder: a preliminary study with transcriptomic perspective |
| title_sort | alteration of il 17 signaling pathway in bipolar disorder a preliminary study with transcriptomic perspective |
| topic | bipolar disorder DEGs (differentially expressed genes) IL-17 pathway immunoinflammatory response immune infiltration analysis |
| url | https://www.frontiersin.org/articles/10.3389/fpsyt.2025.1539038/full |
| work_keys_str_mv | AT xiaobowang thealterationofil17signalingpathwayinbipolardisorderapreliminarystudywithtranscriptomicperspective AT xiaobowang thealterationofil17signalingpathwayinbipolardisorderapreliminarystudywithtranscriptomicperspective AT suyu thealterationofil17signalingpathwayinbipolardisorderapreliminarystudywithtranscriptomicperspective AT zhengao thealterationofil17signalingpathwayinbipolardisorderapreliminarystudywithtranscriptomicperspective AT fangmingxu thealterationofil17signalingpathwayinbipolardisorderapreliminarystudywithtranscriptomicperspective AT yumeiwang thealterationofil17signalingpathwayinbipolardisorderapreliminarystudywithtranscriptomicperspective AT yumeiwang thealterationofil17signalingpathwayinbipolardisorderapreliminarystudywithtranscriptomicperspective AT yumeiwang thealterationofil17signalingpathwayinbipolardisorderapreliminarystudywithtranscriptomicperspective AT tianlezhang thealterationofil17signalingpathwayinbipolardisorderapreliminarystudywithtranscriptomicperspective AT tingtingxie thealterationofil17signalingpathwayinbipolardisorderapreliminarystudywithtranscriptomicperspective AT xihuajia thealterationofil17signalingpathwayinbipolardisorderapreliminarystudywithtranscriptomicperspective AT xiaobowang alterationofil17signalingpathwayinbipolardisorderapreliminarystudywithtranscriptomicperspective AT xiaobowang alterationofil17signalingpathwayinbipolardisorderapreliminarystudywithtranscriptomicperspective AT suyu alterationofil17signalingpathwayinbipolardisorderapreliminarystudywithtranscriptomicperspective AT zhengao alterationofil17signalingpathwayinbipolardisorderapreliminarystudywithtranscriptomicperspective AT fangmingxu alterationofil17signalingpathwayinbipolardisorderapreliminarystudywithtranscriptomicperspective AT yumeiwang alterationofil17signalingpathwayinbipolardisorderapreliminarystudywithtranscriptomicperspective AT yumeiwang alterationofil17signalingpathwayinbipolardisorderapreliminarystudywithtranscriptomicperspective AT yumeiwang alterationofil17signalingpathwayinbipolardisorderapreliminarystudywithtranscriptomicperspective AT tianlezhang alterationofil17signalingpathwayinbipolardisorderapreliminarystudywithtranscriptomicperspective AT tingtingxie alterationofil17signalingpathwayinbipolardisorderapreliminarystudywithtranscriptomicperspective AT xihuajia alterationofil17signalingpathwayinbipolardisorderapreliminarystudywithtranscriptomicperspective |