Regulatory T cells decrease C3-positive reactive astrocytes in Alzheimer-like pathology
Abstract Background Increasing evidence supports a key role for peripheral immune processes in the pathophysiology of Alzheimer’s disease (AD), highlighting an intricate interplay between brain resident glial cells and both innate and adaptive peripheral immune effectors. We previously showed that r...
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| Format: | Article |
| Language: | English |
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BMC
2023-03-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12974-023-02702-3 |
| _version_ | 1797864017030545408 |
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| author | Grégoire Stym-Popper Karen Matta Thomas Chaigneau Roshan Rupra Alexandros Demetriou Stéphane Fouquet Cira Dansokho Cécile Toly-Ndour Guillaume Dorothée |
| author_facet | Grégoire Stym-Popper Karen Matta Thomas Chaigneau Roshan Rupra Alexandros Demetriou Stéphane Fouquet Cira Dansokho Cécile Toly-Ndour Guillaume Dorothée |
| author_sort | Grégoire Stym-Popper |
| collection | DOAJ |
| description | Abstract Background Increasing evidence supports a key role for peripheral immune processes in the pathophysiology of Alzheimer’s disease (AD), highlighting an intricate interplay between brain resident glial cells and both innate and adaptive peripheral immune effectors. We previously showed that regulatory T cells (Tregs) have a beneficial impact on disease progression in AD-like pathology, notably by modulating the microglial response associated with Aβ deposits in a mouse model of amyloid pathology. Besides microglia, reactive astrocytes also play a critical role in neuroinflammatory processes associated with AD. Different phenotypes of reactive astrocytes have previously been characterized, including A1-like neurotoxic and A2-like neuroprotective subtypes. However, the precise impact of Tregs on astrocyte reactivity and phenotypes in AD still remains poorly defined. Methods We assessed the impact of Treg immunomodulation on astrocyte reactivity in a mouse model of AD-like amyloid pathology. Using 3D imaging, we carried out extensive morphological analyses of astrocytes following either depletion or amplification of Tregs. We further assessed the expression of several A1- and A2-like markers by immunofluorescence and RT-qPCR. Results Modulation of Tregs did not significantly impact the magnitude of global astrocyte reactivity in the brain nor in the close vicinity of cortical amyloid deposits. We did not observe changes in the number, morphology, or branching complexity of astrocytes according to immunomodulation of Tregs. However, early transient depletion of Tregs modulated the balance of reactive astrocyte subtypes, resulting in increased C3-positive A1-like phenotypes associated with amyloid deposits. Conversely, early depletion of Tregs decreased markers of A2-like phenotypes of reactive astrocytes associated with larger amyloid deposits. Intriguingly, modulation of Tregs also impacted the cerebral expression of several markers of A1-like subsets in healthy mice. Conclusions Our study suggests that Tregs contribute to modulate and fine-tune the balance of reactive astrocyte subtypes in AD-like amyloid pathology, by dampening C3-positive astrocytes in favor of A2-like phenotypes. This effect of Tregs may partly relate to their capacity at modulating steady state astrocyte reactivity and homeostasis. Our data further highlight the need for refined markers of astrocytes subsets and strategy of analysis for better deciphering the complexity of astrocyte reactivity in neurodegeneration. |
| first_indexed | 2024-04-09T22:44:49Z |
| format | Article |
| id | doaj.art-64a096bf2ec7416ea972fcbbfee59b49 |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-04-09T22:44:49Z |
| publishDate | 2023-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-64a096bf2ec7416ea972fcbbfee59b492023-03-22T11:55:03ZengBMCJournal of Neuroinflammation1742-20942023-03-0120111710.1186/s12974-023-02702-3Regulatory T cells decrease C3-positive reactive astrocytes in Alzheimer-like pathologyGrégoire Stym-Popper0Karen Matta1Thomas Chaigneau2Roshan Rupra3Alexandros Demetriou4Stéphane Fouquet5Cira Dansokho6Cécile Toly-Ndour7Guillaume Dorothée8Sorbonne Université, INSERM UMRS 938, Centre de Recherche Saint-Antoine, CRSA, Immune System and Neuroinflammation Laboratory, Hôpital Saint-AntoineSorbonne Université, INSERM UMRS 938, Centre de Recherche Saint-Antoine, CRSA, Immune System and Neuroinflammation Laboratory, Hôpital Saint-AntoineSorbonne Université, INSERM UMRS 938, Centre de Recherche Saint-Antoine, CRSA, Immune System and Neuroinflammation Laboratory, Hôpital Saint-AntoineSorbonne Université, INSERM UMRS 938, Centre de Recherche Saint-Antoine, CRSA, Immune System and Neuroinflammation Laboratory, Hôpital Saint-AntoineSorbonne Université, INSERM UMRS 938, Centre de Recherche Saint-Antoine, CRSA, Immune System and Neuroinflammation Laboratory, Hôpital Saint-AntoineImaging Platform, Sorbonne Université, INSERM UMR_S968 and CNRS UMR7210, Institut de la VisionSorbonne Université, INSERM UMRS 938, Centre de Recherche Saint-Antoine, CRSA, Immune System and Neuroinflammation Laboratory, Hôpital Saint-AntoineSorbonne Université, INSERM UMRS 938, Centre de Recherche Saint-Antoine, CRSA, Immune System and Neuroinflammation Laboratory, Hôpital Saint-AntoineSorbonne Université, INSERM UMRS 938, Centre de Recherche Saint-Antoine, CRSA, Immune System and Neuroinflammation Laboratory, Hôpital Saint-AntoineAbstract Background Increasing evidence supports a key role for peripheral immune processes in the pathophysiology of Alzheimer’s disease (AD), highlighting an intricate interplay between brain resident glial cells and both innate and adaptive peripheral immune effectors. We previously showed that regulatory T cells (Tregs) have a beneficial impact on disease progression in AD-like pathology, notably by modulating the microglial response associated with Aβ deposits in a mouse model of amyloid pathology. Besides microglia, reactive astrocytes also play a critical role in neuroinflammatory processes associated with AD. Different phenotypes of reactive astrocytes have previously been characterized, including A1-like neurotoxic and A2-like neuroprotective subtypes. However, the precise impact of Tregs on astrocyte reactivity and phenotypes in AD still remains poorly defined. Methods We assessed the impact of Treg immunomodulation on astrocyte reactivity in a mouse model of AD-like amyloid pathology. Using 3D imaging, we carried out extensive morphological analyses of astrocytes following either depletion or amplification of Tregs. We further assessed the expression of several A1- and A2-like markers by immunofluorescence and RT-qPCR. Results Modulation of Tregs did not significantly impact the magnitude of global astrocyte reactivity in the brain nor in the close vicinity of cortical amyloid deposits. We did not observe changes in the number, morphology, or branching complexity of astrocytes according to immunomodulation of Tregs. However, early transient depletion of Tregs modulated the balance of reactive astrocyte subtypes, resulting in increased C3-positive A1-like phenotypes associated with amyloid deposits. Conversely, early depletion of Tregs decreased markers of A2-like phenotypes of reactive astrocytes associated with larger amyloid deposits. Intriguingly, modulation of Tregs also impacted the cerebral expression of several markers of A1-like subsets in healthy mice. Conclusions Our study suggests that Tregs contribute to modulate and fine-tune the balance of reactive astrocyte subtypes in AD-like amyloid pathology, by dampening C3-positive astrocytes in favor of A2-like phenotypes. This effect of Tregs may partly relate to their capacity at modulating steady state astrocyte reactivity and homeostasis. Our data further highlight the need for refined markers of astrocytes subsets and strategy of analysis for better deciphering the complexity of astrocyte reactivity in neurodegeneration.https://doi.org/10.1186/s12974-023-02702-3AstrocytesRegulatory T cellsNeuroinflammationAlzheimer’s disease |
| spellingShingle | Grégoire Stym-Popper Karen Matta Thomas Chaigneau Roshan Rupra Alexandros Demetriou Stéphane Fouquet Cira Dansokho Cécile Toly-Ndour Guillaume Dorothée Regulatory T cells decrease C3-positive reactive astrocytes in Alzheimer-like pathology Journal of Neuroinflammation Astrocytes Regulatory T cells Neuroinflammation Alzheimer’s disease |
| title | Regulatory T cells decrease C3-positive reactive astrocytes in Alzheimer-like pathology |
| title_full | Regulatory T cells decrease C3-positive reactive astrocytes in Alzheimer-like pathology |
| title_fullStr | Regulatory T cells decrease C3-positive reactive astrocytes in Alzheimer-like pathology |
| title_full_unstemmed | Regulatory T cells decrease C3-positive reactive astrocytes in Alzheimer-like pathology |
| title_short | Regulatory T cells decrease C3-positive reactive astrocytes in Alzheimer-like pathology |
| title_sort | regulatory t cells decrease c3 positive reactive astrocytes in alzheimer like pathology |
| topic | Astrocytes Regulatory T cells Neuroinflammation Alzheimer’s disease |
| url | https://doi.org/10.1186/s12974-023-02702-3 |
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