Regulatory T Cells Secrete IL10 to Suppress Neuroinflammation in Early Stage after Subarachnoid Hemorrhage
<i<Objective</i<: Accumulating evidence supports neuroprotective effects of regulatory T cells (Tregs) in response to brain injury. However, the precise mechanisms underlying the beneficial effects of Tregs on suppressing neuroinflammation after subarachnoid hemorrhage (SAH) remain uncle...
Ausführliche Beschreibung
Autor*in: |
Jingyi Zhou [verfasserIn] Fan Yang [verfasserIn] Huaming Li [verfasserIn] Penglei Xu [verfasserIn] Zefeng Wang [verfasserIn] Fangjie Shao [verfasserIn] Anwen Shao [verfasserIn] Jianmin Zhang [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2023 |
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Übergeordnetes Werk: |
In: Medicina - MDPI AG, 2016, 59(2023), 7, p 1317 |
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Übergeordnetes Werk: |
volume:59 ; year:2023 ; number:7, p 1317 |
Links: |
Link aufrufen |
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DOI / URN: |
10.3390/medicina59071317 |
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Katalog-ID: |
DOAJ093862946 |
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520 | |a <i<Objective</i<: Accumulating evidence supports neuroprotective effects of regulatory T cells (Tregs) in response to brain injury. However, the precise mechanisms underlying the beneficial effects of Tregs on suppressing neuroinflammation after subarachnoid hemorrhage (SAH) remain unclear. <i<Methods</i<: We performed flow cytometry to detect the infiltration of Tregs into the brain at different time points after SAH. Behavioral tests, including Adhesive and Rotarod, were performed to assess neurological deficits in mice after SAH. Bulk RNA sequencing was used to investigate the transcriptomic change of Tregs infiltrating into the brain after SAH. qPCR was performed to verify the variation of inflammatory cytokines expression in the brain after Tregs exogenous infusion. FoxP3-DTR mice and Il10 gene KO mice were used to explore the mechanism of Tregs inhibiting neuron apoptosis after infiltrating the brain following SAH onset. <i<Results</i<: Peripheral Tregs infiltrated into the brain one day after SAH and gradually accumulated in the hemorrhagic hemisphere. An exogenous infusion of Tregs significantly improved the neurological function of mice after SAH, while poor recovery of neurological function was observed in Tregs depletion mice. Transcriptome sequencing data suggested that the immunosuppressive function of brain-infiltrated Tregs was significantly upregulated. qPCR showed that the expression of pro-inflammatory cytokines decreased in the brain of SAH mice after exogenous Tregs infusion. Bioinformatic analysis revealed that IL-10 and other cytokines secreted by brain-infiltrated Tregs were upregulated after SAH. Moreover, exogenous infusion of Il10 gene KO Tregs did not totally improve neurological function in SAH mice. <i<Conclusions</i<: Tregs infiltrated into the brain in the early stage after SAH and exerted neuroprotective effect by secreting IL-10 to suppress neuroinflammation and reduce neuron apoptosis. | ||
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10.3390/medicina59071317 doi (DE-627)DOAJ093862946 (DE-599)DOAJ1137cb7013724542954b32b59c34209a DE-627 ger DE-627 rakwb eng R5-920 Jingyi Zhou verfasserin aut Regulatory T Cells Secrete IL10 to Suppress Neuroinflammation in Early Stage after Subarachnoid Hemorrhage 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <i<Objective</i<: Accumulating evidence supports neuroprotective effects of regulatory T cells (Tregs) in response to brain injury. However, the precise mechanisms underlying the beneficial effects of Tregs on suppressing neuroinflammation after subarachnoid hemorrhage (SAH) remain unclear. <i<Methods</i<: We performed flow cytometry to detect the infiltration of Tregs into the brain at different time points after SAH. Behavioral tests, including Adhesive and Rotarod, were performed to assess neurological deficits in mice after SAH. Bulk RNA sequencing was used to investigate the transcriptomic change of Tregs infiltrating into the brain after SAH. qPCR was performed to verify the variation of inflammatory cytokines expression in the brain after Tregs exogenous infusion. FoxP3-DTR mice and Il10 gene KO mice were used to explore the mechanism of Tregs inhibiting neuron apoptosis after infiltrating the brain following SAH onset. <i<Results</i<: Peripheral Tregs infiltrated into the brain one day after SAH and gradually accumulated in the hemorrhagic hemisphere. An exogenous infusion of Tregs significantly improved the neurological function of mice after SAH, while poor recovery of neurological function was observed in Tregs depletion mice. Transcriptome sequencing data suggested that the immunosuppressive function of brain-infiltrated Tregs was significantly upregulated. qPCR showed that the expression of pro-inflammatory cytokines decreased in the brain of SAH mice after exogenous Tregs infusion. Bioinformatic analysis revealed that IL-10 and other cytokines secreted by brain-infiltrated Tregs were upregulated after SAH. Moreover, exogenous infusion of Il10 gene KO Tregs did not totally improve neurological function in SAH mice. <i<Conclusions</i<: Tregs infiltrated into the brain in the early stage after SAH and exerted neuroprotective effect by secreting IL-10 to suppress neuroinflammation and reduce neuron apoptosis. subarachnoid hemorrhage regulatory T cell neuroprotection IL10 neuroinflammation Medicine (General) Fan Yang verfasserin aut Huaming Li verfasserin aut Penglei Xu verfasserin aut Zefeng Wang verfasserin aut Fangjie Shao verfasserin aut Anwen Shao verfasserin aut Jianmin Zhang verfasserin aut In Medicina MDPI AG, 2016 59(2023), 7, p 1317 (DE-627)354543296 (DE-600)2088820-X 16489144 nnns volume:59 year:2023 number:7, p 1317 https://doi.org/10.3390/medicina59071317 kostenfrei https://doaj.org/article/1137cb7013724542954b32b59c34209a kostenfrei https://www.mdpi.com/1648-9144/59/7/1317 kostenfrei https://doaj.org/toc/1010-660X Journal toc kostenfrei https://doaj.org/toc/1648-9144 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 59 2023 7, p 1317 |
spelling |
10.3390/medicina59071317 doi (DE-627)DOAJ093862946 (DE-599)DOAJ1137cb7013724542954b32b59c34209a DE-627 ger DE-627 rakwb eng R5-920 Jingyi Zhou verfasserin aut Regulatory T Cells Secrete IL10 to Suppress Neuroinflammation in Early Stage after Subarachnoid Hemorrhage 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <i<Objective</i<: Accumulating evidence supports neuroprotective effects of regulatory T cells (Tregs) in response to brain injury. However, the precise mechanisms underlying the beneficial effects of Tregs on suppressing neuroinflammation after subarachnoid hemorrhage (SAH) remain unclear. <i<Methods</i<: We performed flow cytometry to detect the infiltration of Tregs into the brain at different time points after SAH. Behavioral tests, including Adhesive and Rotarod, were performed to assess neurological deficits in mice after SAH. Bulk RNA sequencing was used to investigate the transcriptomic change of Tregs infiltrating into the brain after SAH. qPCR was performed to verify the variation of inflammatory cytokines expression in the brain after Tregs exogenous infusion. FoxP3-DTR mice and Il10 gene KO mice were used to explore the mechanism of Tregs inhibiting neuron apoptosis after infiltrating the brain following SAH onset. <i<Results</i<: Peripheral Tregs infiltrated into the brain one day after SAH and gradually accumulated in the hemorrhagic hemisphere. An exogenous infusion of Tregs significantly improved the neurological function of mice after SAH, while poor recovery of neurological function was observed in Tregs depletion mice. Transcriptome sequencing data suggested that the immunosuppressive function of brain-infiltrated Tregs was significantly upregulated. qPCR showed that the expression of pro-inflammatory cytokines decreased in the brain of SAH mice after exogenous Tregs infusion. Bioinformatic analysis revealed that IL-10 and other cytokines secreted by brain-infiltrated Tregs were upregulated after SAH. Moreover, exogenous infusion of Il10 gene KO Tregs did not totally improve neurological function in SAH mice. <i<Conclusions</i<: Tregs infiltrated into the brain in the early stage after SAH and exerted neuroprotective effect by secreting IL-10 to suppress neuroinflammation and reduce neuron apoptosis. subarachnoid hemorrhage regulatory T cell neuroprotection IL10 neuroinflammation Medicine (General) Fan Yang verfasserin aut Huaming Li verfasserin aut Penglei Xu verfasserin aut Zefeng Wang verfasserin aut Fangjie Shao verfasserin aut Anwen Shao verfasserin aut Jianmin Zhang verfasserin aut In Medicina MDPI AG, 2016 59(2023), 7, p 1317 (DE-627)354543296 (DE-600)2088820-X 16489144 nnns volume:59 year:2023 number:7, p 1317 https://doi.org/10.3390/medicina59071317 kostenfrei https://doaj.org/article/1137cb7013724542954b32b59c34209a kostenfrei https://www.mdpi.com/1648-9144/59/7/1317 kostenfrei https://doaj.org/toc/1010-660X Journal toc kostenfrei https://doaj.org/toc/1648-9144 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 59 2023 7, p 1317 |
allfields_unstemmed |
10.3390/medicina59071317 doi (DE-627)DOAJ093862946 (DE-599)DOAJ1137cb7013724542954b32b59c34209a DE-627 ger DE-627 rakwb eng R5-920 Jingyi Zhou verfasserin aut Regulatory T Cells Secrete IL10 to Suppress Neuroinflammation in Early Stage after Subarachnoid Hemorrhage 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <i<Objective</i<: Accumulating evidence supports neuroprotective effects of regulatory T cells (Tregs) in response to brain injury. However, the precise mechanisms underlying the beneficial effects of Tregs on suppressing neuroinflammation after subarachnoid hemorrhage (SAH) remain unclear. <i<Methods</i<: We performed flow cytometry to detect the infiltration of Tregs into the brain at different time points after SAH. Behavioral tests, including Adhesive and Rotarod, were performed to assess neurological deficits in mice after SAH. Bulk RNA sequencing was used to investigate the transcriptomic change of Tregs infiltrating into the brain after SAH. qPCR was performed to verify the variation of inflammatory cytokines expression in the brain after Tregs exogenous infusion. FoxP3-DTR mice and Il10 gene KO mice were used to explore the mechanism of Tregs inhibiting neuron apoptosis after infiltrating the brain following SAH onset. <i<Results</i<: Peripheral Tregs infiltrated into the brain one day after SAH and gradually accumulated in the hemorrhagic hemisphere. An exogenous infusion of Tregs significantly improved the neurological function of mice after SAH, while poor recovery of neurological function was observed in Tregs depletion mice. Transcriptome sequencing data suggested that the immunosuppressive function of brain-infiltrated Tregs was significantly upregulated. qPCR showed that the expression of pro-inflammatory cytokines decreased in the brain of SAH mice after exogenous Tregs infusion. Bioinformatic analysis revealed that IL-10 and other cytokines secreted by brain-infiltrated Tregs were upregulated after SAH. Moreover, exogenous infusion of Il10 gene KO Tregs did not totally improve neurological function in SAH mice. <i<Conclusions</i<: Tregs infiltrated into the brain in the early stage after SAH and exerted neuroprotective effect by secreting IL-10 to suppress neuroinflammation and reduce neuron apoptosis. subarachnoid hemorrhage regulatory T cell neuroprotection IL10 neuroinflammation Medicine (General) Fan Yang verfasserin aut Huaming Li verfasserin aut Penglei Xu verfasserin aut Zefeng Wang verfasserin aut Fangjie Shao verfasserin aut Anwen Shao verfasserin aut Jianmin Zhang verfasserin aut In Medicina MDPI AG, 2016 59(2023), 7, p 1317 (DE-627)354543296 (DE-600)2088820-X 16489144 nnns volume:59 year:2023 number:7, p 1317 https://doi.org/10.3390/medicina59071317 kostenfrei https://doaj.org/article/1137cb7013724542954b32b59c34209a kostenfrei https://www.mdpi.com/1648-9144/59/7/1317 kostenfrei https://doaj.org/toc/1010-660X Journal toc kostenfrei https://doaj.org/toc/1648-9144 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 59 2023 7, p 1317 |
allfieldsGer |
10.3390/medicina59071317 doi (DE-627)DOAJ093862946 (DE-599)DOAJ1137cb7013724542954b32b59c34209a DE-627 ger DE-627 rakwb eng R5-920 Jingyi Zhou verfasserin aut Regulatory T Cells Secrete IL10 to Suppress Neuroinflammation in Early Stage after Subarachnoid Hemorrhage 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <i<Objective</i<: Accumulating evidence supports neuroprotective effects of regulatory T cells (Tregs) in response to brain injury. However, the precise mechanisms underlying the beneficial effects of Tregs on suppressing neuroinflammation after subarachnoid hemorrhage (SAH) remain unclear. <i<Methods</i<: We performed flow cytometry to detect the infiltration of Tregs into the brain at different time points after SAH. Behavioral tests, including Adhesive and Rotarod, were performed to assess neurological deficits in mice after SAH. Bulk RNA sequencing was used to investigate the transcriptomic change of Tregs infiltrating into the brain after SAH. qPCR was performed to verify the variation of inflammatory cytokines expression in the brain after Tregs exogenous infusion. FoxP3-DTR mice and Il10 gene KO mice were used to explore the mechanism of Tregs inhibiting neuron apoptosis after infiltrating the brain following SAH onset. <i<Results</i<: Peripheral Tregs infiltrated into the brain one day after SAH and gradually accumulated in the hemorrhagic hemisphere. An exogenous infusion of Tregs significantly improved the neurological function of mice after SAH, while poor recovery of neurological function was observed in Tregs depletion mice. Transcriptome sequencing data suggested that the immunosuppressive function of brain-infiltrated Tregs was significantly upregulated. qPCR showed that the expression of pro-inflammatory cytokines decreased in the brain of SAH mice after exogenous Tregs infusion. Bioinformatic analysis revealed that IL-10 and other cytokines secreted by brain-infiltrated Tregs were upregulated after SAH. Moreover, exogenous infusion of Il10 gene KO Tregs did not totally improve neurological function in SAH mice. <i<Conclusions</i<: Tregs infiltrated into the brain in the early stage after SAH and exerted neuroprotective effect by secreting IL-10 to suppress neuroinflammation and reduce neuron apoptosis. subarachnoid hemorrhage regulatory T cell neuroprotection IL10 neuroinflammation Medicine (General) Fan Yang verfasserin aut Huaming Li verfasserin aut Penglei Xu verfasserin aut Zefeng Wang verfasserin aut Fangjie Shao verfasserin aut Anwen Shao verfasserin aut Jianmin Zhang verfasserin aut In Medicina MDPI AG, 2016 59(2023), 7, p 1317 (DE-627)354543296 (DE-600)2088820-X 16489144 nnns volume:59 year:2023 number:7, p 1317 https://doi.org/10.3390/medicina59071317 kostenfrei https://doaj.org/article/1137cb7013724542954b32b59c34209a kostenfrei https://www.mdpi.com/1648-9144/59/7/1317 kostenfrei https://doaj.org/toc/1010-660X Journal toc kostenfrei https://doaj.org/toc/1648-9144 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 59 2023 7, p 1317 |
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10.3390/medicina59071317 doi (DE-627)DOAJ093862946 (DE-599)DOAJ1137cb7013724542954b32b59c34209a DE-627 ger DE-627 rakwb eng R5-920 Jingyi Zhou verfasserin aut Regulatory T Cells Secrete IL10 to Suppress Neuroinflammation in Early Stage after Subarachnoid Hemorrhage 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <i<Objective</i<: Accumulating evidence supports neuroprotective effects of regulatory T cells (Tregs) in response to brain injury. However, the precise mechanisms underlying the beneficial effects of Tregs on suppressing neuroinflammation after subarachnoid hemorrhage (SAH) remain unclear. <i<Methods</i<: We performed flow cytometry to detect the infiltration of Tregs into the brain at different time points after SAH. Behavioral tests, including Adhesive and Rotarod, were performed to assess neurological deficits in mice after SAH. Bulk RNA sequencing was used to investigate the transcriptomic change of Tregs infiltrating into the brain after SAH. qPCR was performed to verify the variation of inflammatory cytokines expression in the brain after Tregs exogenous infusion. FoxP3-DTR mice and Il10 gene KO mice were used to explore the mechanism of Tregs inhibiting neuron apoptosis after infiltrating the brain following SAH onset. <i<Results</i<: Peripheral Tregs infiltrated into the brain one day after SAH and gradually accumulated in the hemorrhagic hemisphere. An exogenous infusion of Tregs significantly improved the neurological function of mice after SAH, while poor recovery of neurological function was observed in Tregs depletion mice. Transcriptome sequencing data suggested that the immunosuppressive function of brain-infiltrated Tregs was significantly upregulated. qPCR showed that the expression of pro-inflammatory cytokines decreased in the brain of SAH mice after exogenous Tregs infusion. Bioinformatic analysis revealed that IL-10 and other cytokines secreted by brain-infiltrated Tregs were upregulated after SAH. Moreover, exogenous infusion of Il10 gene KO Tregs did not totally improve neurological function in SAH mice. <i<Conclusions</i<: Tregs infiltrated into the brain in the early stage after SAH and exerted neuroprotective effect by secreting IL-10 to suppress neuroinflammation and reduce neuron apoptosis. subarachnoid hemorrhage regulatory T cell neuroprotection IL10 neuroinflammation Medicine (General) Fan Yang verfasserin aut Huaming Li verfasserin aut Penglei Xu verfasserin aut Zefeng Wang verfasserin aut Fangjie Shao verfasserin aut Anwen Shao verfasserin aut Jianmin Zhang verfasserin aut In Medicina MDPI AG, 2016 59(2023), 7, p 1317 (DE-627)354543296 (DE-600)2088820-X 16489144 nnns volume:59 year:2023 number:7, p 1317 https://doi.org/10.3390/medicina59071317 kostenfrei https://doaj.org/article/1137cb7013724542954b32b59c34209a kostenfrei https://www.mdpi.com/1648-9144/59/7/1317 kostenfrei https://doaj.org/toc/1010-660X Journal toc kostenfrei https://doaj.org/toc/1648-9144 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 59 2023 7, p 1317 |
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<i<Objective</i<: Accumulating evidence supports neuroprotective effects of regulatory T cells (Tregs) in response to brain injury. However, the precise mechanisms underlying the beneficial effects of Tregs on suppressing neuroinflammation after subarachnoid hemorrhage (SAH) remain unclear. <i<Methods</i<: We performed flow cytometry to detect the infiltration of Tregs into the brain at different time points after SAH. Behavioral tests, including Adhesive and Rotarod, were performed to assess neurological deficits in mice after SAH. Bulk RNA sequencing was used to investigate the transcriptomic change of Tregs infiltrating into the brain after SAH. qPCR was performed to verify the variation of inflammatory cytokines expression in the brain after Tregs exogenous infusion. FoxP3-DTR mice and Il10 gene KO mice were used to explore the mechanism of Tregs inhibiting neuron apoptosis after infiltrating the brain following SAH onset. <i<Results</i<: Peripheral Tregs infiltrated into the brain one day after SAH and gradually accumulated in the hemorrhagic hemisphere. An exogenous infusion of Tregs significantly improved the neurological function of mice after SAH, while poor recovery of neurological function was observed in Tregs depletion mice. Transcriptome sequencing data suggested that the immunosuppressive function of brain-infiltrated Tregs was significantly upregulated. qPCR showed that the expression of pro-inflammatory cytokines decreased in the brain of SAH mice after exogenous Tregs infusion. Bioinformatic analysis revealed that IL-10 and other cytokines secreted by brain-infiltrated Tregs were upregulated after SAH. Moreover, exogenous infusion of Il10 gene KO Tregs did not totally improve neurological function in SAH mice. <i<Conclusions</i<: Tregs infiltrated into the brain in the early stage after SAH and exerted neuroprotective effect by secreting IL-10 to suppress neuroinflammation and reduce neuron apoptosis. |
abstractGer |
<i<Objective</i<: Accumulating evidence supports neuroprotective effects of regulatory T cells (Tregs) in response to brain injury. However, the precise mechanisms underlying the beneficial effects of Tregs on suppressing neuroinflammation after subarachnoid hemorrhage (SAH) remain unclear. <i<Methods</i<: We performed flow cytometry to detect the infiltration of Tregs into the brain at different time points after SAH. Behavioral tests, including Adhesive and Rotarod, were performed to assess neurological deficits in mice after SAH. Bulk RNA sequencing was used to investigate the transcriptomic change of Tregs infiltrating into the brain after SAH. qPCR was performed to verify the variation of inflammatory cytokines expression in the brain after Tregs exogenous infusion. FoxP3-DTR mice and Il10 gene KO mice were used to explore the mechanism of Tregs inhibiting neuron apoptosis after infiltrating the brain following SAH onset. <i<Results</i<: Peripheral Tregs infiltrated into the brain one day after SAH and gradually accumulated in the hemorrhagic hemisphere. An exogenous infusion of Tregs significantly improved the neurological function of mice after SAH, while poor recovery of neurological function was observed in Tregs depletion mice. Transcriptome sequencing data suggested that the immunosuppressive function of brain-infiltrated Tregs was significantly upregulated. qPCR showed that the expression of pro-inflammatory cytokines decreased in the brain of SAH mice after exogenous Tregs infusion. Bioinformatic analysis revealed that IL-10 and other cytokines secreted by brain-infiltrated Tregs were upregulated after SAH. Moreover, exogenous infusion of Il10 gene KO Tregs did not totally improve neurological function in SAH mice. <i<Conclusions</i<: Tregs infiltrated into the brain in the early stage after SAH and exerted neuroprotective effect by secreting IL-10 to suppress neuroinflammation and reduce neuron apoptosis. |
abstract_unstemmed |
<i<Objective</i<: Accumulating evidence supports neuroprotective effects of regulatory T cells (Tregs) in response to brain injury. However, the precise mechanisms underlying the beneficial effects of Tregs on suppressing neuroinflammation after subarachnoid hemorrhage (SAH) remain unclear. <i<Methods</i<: We performed flow cytometry to detect the infiltration of Tregs into the brain at different time points after SAH. Behavioral tests, including Adhesive and Rotarod, were performed to assess neurological deficits in mice after SAH. Bulk RNA sequencing was used to investigate the transcriptomic change of Tregs infiltrating into the brain after SAH. qPCR was performed to verify the variation of inflammatory cytokines expression in the brain after Tregs exogenous infusion. FoxP3-DTR mice and Il10 gene KO mice were used to explore the mechanism of Tregs inhibiting neuron apoptosis after infiltrating the brain following SAH onset. <i<Results</i<: Peripheral Tregs infiltrated into the brain one day after SAH and gradually accumulated in the hemorrhagic hemisphere. An exogenous infusion of Tregs significantly improved the neurological function of mice after SAH, while poor recovery of neurological function was observed in Tregs depletion mice. Transcriptome sequencing data suggested that the immunosuppressive function of brain-infiltrated Tregs was significantly upregulated. qPCR showed that the expression of pro-inflammatory cytokines decreased in the brain of SAH mice after exogenous Tregs infusion. Bioinformatic analysis revealed that IL-10 and other cytokines secreted by brain-infiltrated Tregs were upregulated after SAH. Moreover, exogenous infusion of Il10 gene KO Tregs did not totally improve neurological function in SAH mice. <i<Conclusions</i<: Tregs infiltrated into the brain in the early stage after SAH and exerted neuroprotective effect by secreting IL-10 to suppress neuroinflammation and reduce neuron apoptosis. |
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7, p 1317 |
title_short |
Regulatory T Cells Secrete IL10 to Suppress Neuroinflammation in Early Stage after Subarachnoid Hemorrhage |
url |
https://doi.org/10.3390/medicina59071317 https://doaj.org/article/1137cb7013724542954b32b59c34209a https://www.mdpi.com/1648-9144/59/7/1317 https://doaj.org/toc/1010-660X https://doaj.org/toc/1648-9144 |
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Fan Yang Huaming Li Penglei Xu Zefeng Wang Fangjie Shao Anwen Shao Jianmin Zhang |
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Fan Yang Huaming Li Penglei Xu Zefeng Wang Fangjie Shao Anwen Shao Jianmin Zhang |
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