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CD4+ T cells contribute to neurodegeneration in Lewy body dementia.

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Title: CD4+ T cells contribute to neurodegeneration in Lewy body dementia.
Authors: Gate, David, Tapp, Emma, Leventhal, Olivia, Shahid, Marian, Nonninger, Tim J., Yang, Andrew C., Strempfl, Katharina, Unger, Michael S., Fehlmann, Tobias, Oh, Hamilton, Channappa, Divya, Henderson, Victor W., Keller, Andreas, Aigner, Ludwig, Galasko, Douglas R., Davis, Mark M., Poston, Kathleen L., Wyss-Coray, Tony
Source: Science (pre-March 2025). 11/12/2021, Vol. 374 Issue 6569, p868-874. 7p. 5 Diagrams.
Subjects: Immune system, Neurodegeneration, Lewy body dementia, Chemokines, T cells
Abstract: Recent studies indicate that the adaptive immune system plays a role in Lewy body dementia (LBD). However, the mechanism regulating T cell brain homing in LBD is unknown. Here, we observed T cells adjacent to Lewy bodies and dopaminergic neurons in postmortem LBD brains. Single-cell RNA sequencing of cerebrospinal fluid (CSF) identified up-regulated expression of C-X-C motif chemokine receptor 4 (CXCR4) in CD4+ T cells in LBD. CSF protein levels of the CXCR4 ligand, C-X-C motif chemokine ligand 12 (CXCL12), were associated with neuroaxonal damage in LBD. Furthermore, we observed clonal expansion and up-regulated interleukin 17A expression by CD4+ T cells stimulated with a phosphorylated a-synuclein epitope. Thus, CXCR4-CXCL12 signaling may represent a mechanistic target for inhibiting pathological interleukin-17Ðproducing T cell trafficking in LBD. [ABSTRACT FROM AUTHOR]
Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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PubType: Academic Journal
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  Data: CD4+ T cells contribute to neurodegeneration in Lewy body dementia.
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  Data: <searchLink fieldCode="AR" term="%22Gate%2C+David%22">Gate, David</searchLink><br /><searchLink fieldCode="AR" term="%22Tapp%2C+Emma%22">Tapp, Emma</searchLink><br /><searchLink fieldCode="AR" term="%22Leventhal%2C+Olivia%22">Leventhal, Olivia</searchLink><br /><searchLink fieldCode="AR" term="%22Shahid%2C+Marian%22">Shahid, Marian</searchLink><br /><searchLink fieldCode="AR" term="%22Nonninger%2C+Tim+J%2E%22">Nonninger, Tim J.</searchLink><br /><searchLink fieldCode="AR" term="%22Yang%2C+Andrew+C%2E%22">Yang, Andrew C.</searchLink><br /><searchLink fieldCode="AR" term="%22Strempfl%2C+Katharina%22">Strempfl, Katharina</searchLink><br /><searchLink fieldCode="AR" term="%22Unger%2C+Michael+S%2E%22">Unger, Michael S.</searchLink><br /><searchLink fieldCode="AR" term="%22Fehlmann%2C+Tobias%22">Fehlmann, Tobias</searchLink><br /><searchLink fieldCode="AR" term="%22Oh%2C+Hamilton%22">Oh, Hamilton</searchLink><br /><searchLink fieldCode="AR" term="%22Channappa%2C+Divya%22">Channappa, Divya</searchLink><br /><searchLink fieldCode="AR" term="%22Henderson%2C+Victor+W%2E%22">Henderson, Victor W.</searchLink><br /><searchLink fieldCode="AR" term="%22Keller%2C+Andreas%22">Keller, Andreas</searchLink><br /><searchLink fieldCode="AR" term="%22Aigner%2C+Ludwig%22">Aigner, Ludwig</searchLink><br /><searchLink fieldCode="AR" term="%22Galasko%2C+Douglas+R%2E%22">Galasko, Douglas R.</searchLink><br /><searchLink fieldCode="AR" term="%22Davis%2C+Mark+M%2E%22">Davis, Mark M.</searchLink><br /><searchLink fieldCode="AR" term="%22Poston%2C+Kathleen+L%2E%22">Poston, Kathleen L.</searchLink><br /><searchLink fieldCode="AR" term="%22Wyss-Coray%2C+Tony%22">Wyss-Coray, Tony</searchLink>
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  Data: <searchLink fieldCode="JN" term="%22Science+%28pre-March+2025%29%22">Science (pre-March 2025)</searchLink>. 11/12/2021, Vol. 374 Issue 6569, p868-874. 7p. 5 Diagrams.
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  Data: <searchLink fieldCode="DE" term="%22Immune+system%22">Immune system</searchLink><br /><searchLink fieldCode="DE" term="%22Neurodegeneration%22">Neurodegeneration</searchLink><br /><searchLink fieldCode="DE" term="%22Lewy+body+dementia%22">Lewy body dementia</searchLink><br /><searchLink fieldCode="DE" term="%22Chemokines%22">Chemokines</searchLink><br /><searchLink fieldCode="DE" term="%22T+cells%22">T cells</searchLink>
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  Label: Abstract
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  Data: Recent studies indicate that the adaptive immune system plays a role in Lewy body dementia (LBD). However, the mechanism regulating T cell brain homing in LBD is unknown. Here, we observed T cells adjacent to Lewy bodies and dopaminergic neurons in postmortem LBD brains. Single-cell RNA sequencing of cerebrospinal fluid (CSF) identified up-regulated expression of C-X-C motif chemokine receptor 4 (CXCR4) in CD4+ T cells in LBD. CSF protein levels of the CXCR4 ligand, C-X-C motif chemokine ligand 12 (CXCL12), were associated with neuroaxonal damage in LBD. Furthermore, we observed clonal expansion and up-regulated interleukin 17A expression by CD4+ T cells stimulated with a phosphorylated a-synuclein epitope. Thus, CXCR4-CXCL12 signaling may represent a mechanistic target for inhibiting pathological interleukin-17Ðproducing T cell trafficking in LBD. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1126/science.abf7266
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        Text: English
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        PageCount: 7
        StartPage: 868
    Subjects:
      – SubjectFull: Immune system
        Type: general
      – SubjectFull: Neurodegeneration
        Type: general
      – SubjectFull: Lewy body dementia
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      – SubjectFull: Chemokines
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      – SubjectFull: T cells
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      – TitleFull: CD4+ T cells contribute to neurodegeneration in Lewy body dementia.
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              Text: 11/12/2021
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