Pathway analysis of peripheral blood CD8+ T cell transcriptome shows differential regulation of sphingolipid signaling in multiple sclerosis and glioblastoma
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Multiple sclerosis (MS) and glioblastoma (GBM) are CNS diseases in whose development and progression immune privilege is intimately important, but in a relatively opposite manner. Maintenance and strengthening of immune privilege have been shown to be an important mechanism in glioblastoma immune evasion, while the breakdown of immune privilege leads to MS initiation and exacerbation. We hypothesize that molecular signaling pathways can be oppositely regulated in peripheral blood CD8+ T cells of MS and glioblastoma patients at a transcriptional level. We analyzed publicly available data of the peripheral blood CD8+ T cell MS vs. control (MSvsCTRL) and GBM vs. control (GBMvsCTRL) differentially expressed gene (DEG) contrasts with Qiagen’s Ingenuity pathway analysis software (IPA). We have identified sphingolipid signaling pathway which was significantly downregulated in the GBMvsCTRL and upregulated in the MSvsCTRL. As the pathway is important for the CD8+ T lymphocytes CNS infiltration..., this result is in line with our previously stated hypothesis. Comparing publicly available lists of differentially expressed serum exosomal miRNAs from MSvsCTRL and GBMvsCTRL contrasts, we have identified that hsa-miR182-5p has the greatest potential effect on sphingolipid signaling regarding the number of regulated DEGs in the GBMvsCTRL contrast, while not being able to find any relevant potential sphingolipid signaling target transcripts in the MSvsCTRL contrast. We conclude that the sphingolipid signaling pathway is a top oppositely regulated pathway in peripheral blood CD8+ T cells from GBM and MS, and might be crucial for the differences in CNS immune privilege maintenance of investigated diseases, but further experimental research is necessary.
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PLoS ONE, 2024, 19, 6, e0305042-
DOI: 10.1371/journal.pone.0305042
ISSN: 1932-6203
PubMed: 38861512
Scopus: 2-s2.0-85195776320
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VinčaTY - JOUR AU - Stefanović, Milan AU - Jovanović, Ivan AU - Živković, Maja AU - Stanković, Aleksandra PY - 2024 UR - https://vinar.vin.bg.ac.rs/handle/123456789/13389 AB - Multiple sclerosis (MS) and glioblastoma (GBM) are CNS diseases in whose development and progression immune privilege is intimately important, but in a relatively opposite manner. Maintenance and strengthening of immune privilege have been shown to be an important mechanism in glioblastoma immune evasion, while the breakdown of immune privilege leads to MS initiation and exacerbation. We hypothesize that molecular signaling pathways can be oppositely regulated in peripheral blood CD8+ T cells of MS and glioblastoma patients at a transcriptional level. We analyzed publicly available data of the peripheral blood CD8+ T cell MS vs. control (MSvsCTRL) and GBM vs. control (GBMvsCTRL) differentially expressed gene (DEG) contrasts with Qiagen’s Ingenuity pathway analysis software (IPA). We have identified sphingolipid signaling pathway which was significantly downregulated in the GBMvsCTRL and upregulated in the MSvsCTRL. As the pathway is important for the CD8+ T lymphocytes CNS infiltration, this result is in line with our previously stated hypothesis. Comparing publicly available lists of differentially expressed serum exosomal miRNAs from MSvsCTRL and GBMvsCTRL contrasts, we have identified that hsa-miR182-5p has the greatest potential effect on sphingolipid signaling regarding the number of regulated DEGs in the GBMvsCTRL contrast, while not being able to find any relevant potential sphingolipid signaling target transcripts in the MSvsCTRL contrast. We conclude that the sphingolipid signaling pathway is a top oppositely regulated pathway in peripheral blood CD8+ T cells from GBM and MS, and might be crucial for the differences in CNS immune privilege maintenance of investigated diseases, but further experimental research is necessary. T2 - PLOS ONE T1 - Pathway analysis of peripheral blood CD8+ T cell transcriptome shows differential regulation of sphingolipid signaling in multiple sclerosis and glioblastoma VL - 19 IS - 6 SP - e0305042 DO - 10.1371/journal.pone.0305042 ER -
@article{ editor = "Sukocheva, Olga A.", author = "Stefanović, Milan and Jovanović, Ivan and Živković, Maja and Stanković, Aleksandra", year = "2024", abstract = "Multiple sclerosis (MS) and glioblastoma (GBM) are CNS diseases in whose development and progression immune privilege is intimately important, but in a relatively opposite manner. Maintenance and strengthening of immune privilege have been shown to be an important mechanism in glioblastoma immune evasion, while the breakdown of immune privilege leads to MS initiation and exacerbation. We hypothesize that molecular signaling pathways can be oppositely regulated in peripheral blood CD8+ T cells of MS and glioblastoma patients at a transcriptional level. We analyzed publicly available data of the peripheral blood CD8+ T cell MS vs. control (MSvsCTRL) and GBM vs. control (GBMvsCTRL) differentially expressed gene (DEG) contrasts with Qiagen’s Ingenuity pathway analysis software (IPA). We have identified sphingolipid signaling pathway which was significantly downregulated in the GBMvsCTRL and upregulated in the MSvsCTRL. As the pathway is important for the CD8+ T lymphocytes CNS infiltration, this result is in line with our previously stated hypothesis. Comparing publicly available lists of differentially expressed serum exosomal miRNAs from MSvsCTRL and GBMvsCTRL contrasts, we have identified that hsa-miR182-5p has the greatest potential effect on sphingolipid signaling regarding the number of regulated DEGs in the GBMvsCTRL contrast, while not being able to find any relevant potential sphingolipid signaling target transcripts in the MSvsCTRL contrast. We conclude that the sphingolipid signaling pathway is a top oppositely regulated pathway in peripheral blood CD8+ T cells from GBM and MS, and might be crucial for the differences in CNS immune privilege maintenance of investigated diseases, but further experimental research is necessary.", journal = "PLOS ONE", title = "Pathway analysis of peripheral blood CD8+ T cell transcriptome shows differential regulation of sphingolipid signaling in multiple sclerosis and glioblastoma", volume = "19", number = "6", pages = "e0305042", doi = "10.1371/journal.pone.0305042" }
Sukocheva, O. A., Stefanović, M., Jovanović, I., Živković, M.,& Stanković, A.. (2024). Pathway analysis of peripheral blood CD8+ T cell transcriptome shows differential regulation of sphingolipid signaling in multiple sclerosis and glioblastoma. in PLOS ONE, 19(6), e0305042. https://doi.org/10.1371/journal.pone.0305042
Sukocheva OA, Stefanović M, Jovanović I, Živković M, Stanković A. Pathway analysis of peripheral blood CD8+ T cell transcriptome shows differential regulation of sphingolipid signaling in multiple sclerosis and glioblastoma. in PLOS ONE. 2024;19(6):e0305042. doi:10.1371/journal.pone.0305042 .
Sukocheva, Olga A., Stefanović, Milan, Jovanović, Ivan, Živković, Maja, Stanković, Aleksandra, "Pathway analysis of peripheral blood CD8+ T cell transcriptome shows differential regulation of sphingolipid signaling in multiple sclerosis and glioblastoma" in PLOS ONE, 19, no. 6 (2024):e0305042, https://doi.org/10.1371/journal.pone.0305042 . .