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Title:
27-hydroxycholesterol causes cognitive deficits by disturbing Th17/Treg balance and the related immune responses in mild cognitive impairment patients and C57BL/6J mice | Journal of Neuroinflammation
Description:
Background Cognitive impairment is associated with dysregulated immune responses. Emerging evidence indicates that Th17 cells and their characteristic cytokine-IL-17 are receiving growing interest in the pathogenesis of cognitive decline. Here, we focus on the involvement of Th17 cells in mild cognitive impairment (MCI) and the possible mechanism of cholesterol metabolite-27-hydroxycholesterol (27-OHC). Methods 100 individuals were recruited into the nested case–control study who completed cognition assessment and the detection of oxysterols and Th17-related cytokines in serum. In addition, mice were treated with 27-OHC and inhibitors of RORγt and Foxp3 (Th17 and Treg transcription factors), and the factors involved in Th17/Treg balance and amyloidosis were detected. Results Our results showed there was enhanced 27-OHC level in serum of MCI individuals. The Th17-related cytokines homeostasis was altered, manifested as increased IL-17A, IL-12p70, IL-23, GM-CSF, MIP-3α and TNF-α but decreased IL-13, IL-28A and TGF-β1. Further, in vivo experiments showed that 27-OHC induced higher immunogenicity, which increased Th17 proportion but decreased Treg cells in peripheral blood mononuclear cells (PBMCs); Th17 proportions in hippocampus, and IL-17A level in serum and brain were also higher than control mice. The fluorescence intensity of amyloid-β (Aβ) and the precursor of amyloid A amyloidosis–serum amyloid A (SAA) was increased in the brain of 27-OHC-treated mice, and worse learning and memory performance was supported by water maze test results. While by inhibiting RORγt in 27-OHC-loaded mice, Th17 proportions in both PBMCs and hippocampus were reduced, and expressions of IL-17A and TGF-β1 were down- and up-regulated, respectively, along with a decreased amyloidosis in brain and improved learning and memory decline. Conclusions Altogether, our results demonstrate that excessive 27-OHC aggravates the amyloidosis and leads to cognitive deficits by regulating RORγt and disturbing Th17/Treg balance.
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Keywords {🔍}
ohc, group, brain, cells, article, pubmed, cognitive, mice, serum, google, scholar, rorγt, saa, level, mci, ila, control, cytokines, compared, fig, expression, cas, study, results, gene, amyloid, protein, threlated, increased, day, impairment, decreased, pbmcs, hippocampus, disease, table, data, thtreg, immune, oxysterols, central, decline, tgfβ, higher, balance, full, amyloidosis, significant, size, wang,
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granulocyte–macrophage colony-stimulating factor 7α-hydroxy-3-oxo-4-cholestenoic acid 3β-hydroxy-5-cholestenoic acid mini-mental state examination th17/treg-related immune responses disturbing th17/treg balance nis-elements viewer v5 article download pdf 27-ohc-induced th17/treg imbalance sandwich-based antibody microarray cultured sh-sy5y cells decreased immuno-suppressive cytokines th17-related cytokines spectrum male c57bl/6j mice central nervous system nested case–control study short-term/working memory indispensable nuclear factor-rorγt quantitative real-time pcr auto-inflammatory neurological disorders facilitating tcr-dependent signaling mild cognitive impairment th17-related immune responses th17-related cytokines homeostasis detect th17-related cytokines rt-qpcr including rorγt 27-ohc promotes amyloid-β serum th17-related cytokines body mass index privacy choices/manage cookies th17/treg balance lower ifn-λ2 gene greater cognitive impairment cognitive impairment caused 27-ohc + sr1001 significantly reduced single 27-ohc-treated group full access th17 cells/il-17a montreal cognitive assessment biotinylated antibody incubation morris water maze earliest symptomatic state state key program western blot results th17-related cytokines endogenous peroxidase activity nat rev neurol jang wy time discrimination index small sample size
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headline:27-hydroxycholesterol causes cognitive deficits by disturbing Th17/Treg balance and the related immune responses in mild cognitive impairment patients and C57BL/6J mice
description:Cognitive impairment is associated with dysregulated immune responses. Emerging evidence indicates that Th17 cells and their characteristic cytokine-IL-17 are receiving growing interest in the pathogenesis of cognitive decline. Here, we focus on the involvement of Th17 cells in mild cognitive impairment (MCI) and the possible mechanism of cholesterol metabolite-27-hydroxycholesterol (27-OHC). 100 individuals were recruited into the nested case–control study who completed cognition assessment and the detection of oxysterols and Th17-related cytokines in serum. In addition, mice were treated with 27-OHC and inhibitors of RORγt and Foxp3 (Th17 and Treg transcription factors), and the factors involved in Th17/Treg balance and amyloidosis were detected. Our results showed there was enhanced 27-OHC level in serum of MCI individuals. The Th17-related cytokines homeostasis was altered, manifested as increased IL-17A, IL-12p70, IL-23, GM-CSF, MIP-3α and TNF-α but decreased IL-13, IL-28A and TGF-β1. Further, in vivo experiments showed that 27-OHC induced higher immunogenicity, which increased Th17 proportion but decreased Treg cells in peripheral blood mononuclear cells (PBMCs); Th17 proportions in hippocampus, and IL-17A level in serum and brain were also higher than control mice. The fluorescence intensity of amyloid-β (Aβ) and the precursor of amyloid A amyloidosis–serum amyloid A (SAA) was increased in the brain of 27-OHC-treated mice, and worse learning and memory performance was supported by water maze test results. While by inhibiting RORγt in 27-OHC-loaded mice, Th17 proportions in both PBMCs and hippocampus were reduced, and expressions of IL-17A and TGF-β1 were down- and up-regulated, respectively, along with a decreased amyloidosis in brain and improved learning and memory decline. Altogether, our results demonstrate that excessive 27-OHC aggravates the amyloidosis and leads to cognitive deficits by regulating RORγt and disturbing Th17/Treg balance.
datePublished:2023-12-19T00:00:00Z
dateModified:2023-12-19T00:00:00Z
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27-hydroxycholesterol
Th17/Treg balance
RORγt
Amyloidosis
Cognitive decline
Neurosciences
Neurology
Neurobiology
Immunology
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headline:27-hydroxycholesterol causes cognitive deficits by disturbing Th17/Treg balance and the related immune responses in mild cognitive impairment patients and C57BL/6J mice
description:Cognitive impairment is associated with dysregulated immune responses. Emerging evidence indicates that Th17 cells and their characteristic cytokine-IL-17 are receiving growing interest in the pathogenesis of cognitive decline. Here, we focus on the involvement of Th17 cells in mild cognitive impairment (MCI) and the possible mechanism of cholesterol metabolite-27-hydroxycholesterol (27-OHC). 100 individuals were recruited into the nested case–control study who completed cognition assessment and the detection of oxysterols and Th17-related cytokines in serum. In addition, mice were treated with 27-OHC and inhibitors of RORγt and Foxp3 (Th17 and Treg transcription factors), and the factors involved in Th17/Treg balance and amyloidosis were detected. Our results showed there was enhanced 27-OHC level in serum of MCI individuals. The Th17-related cytokines homeostasis was altered, manifested as increased IL-17A, IL-12p70, IL-23, GM-CSF, MIP-3α and TNF-α but decreased IL-13, IL-28A and TGF-β1. Further, in vivo experiments showed that 27-OHC induced higher immunogenicity, which increased Th17 proportion but decreased Treg cells in peripheral blood mononuclear cells (PBMCs); Th17 proportions in hippocampus, and IL-17A level in serum and brain were also higher than control mice. The fluorescence intensity of amyloid-β (Aβ) and the precursor of amyloid A amyloidosis–serum amyloid A (SAA) was increased in the brain of 27-OHC-treated mice, and worse learning and memory performance was supported by water maze test results. While by inhibiting RORγt in 27-OHC-loaded mice, Th17 proportions in both PBMCs and hippocampus were reduced, and expressions of IL-17A and TGF-β1 were down- and up-regulated, respectively, along with a decreased amyloidosis in brain and improved learning and memory decline. Altogether, our results demonstrate that excessive 27-OHC aggravates the amyloidosis and leads to cognitive deficits by regulating RORγt and disturbing Th17/Treg balance.
datePublished:2023-12-19T00:00:00Z
dateModified:2023-12-19T00:00:00Z
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27-hydroxycholesterol
Th17/Treg balance
RORγt
Amyloidosis
Cognitive decline
Neurosciences
Neurology
Neurobiology
Immunology
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