Absence of Plekhg5 Results in Myelin Infoldings Corresponding to an Impaired Schwann Cell Autophagy, and a Reduced T-Cell Infiltration Into Peripheral Nerves
Inflammation and dysregulation of the immune system are hallmarks of several neurodegenerative diseases. An activated immune response is considered to be the cause of myelin breakdown in demyelinating disorders. In the peripheral nervous system (PNS), myelin can be degraded in an autophagy-dependent...
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Frontiers Media S.A.
2020-07-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fncel.2020.00185/full |
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doaj-e3f3ff6a74f04927968c9a252e19b9412020-11-25T03:07:14ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022020-07-011410.3389/fncel.2020.00185536851Absence of Plekhg5 Results in Myelin Infoldings Corresponding to an Impaired Schwann Cell Autophagy, and a Reduced T-Cell Infiltration Into Peripheral NervesPatrick Lüningschrör0Carsten Slotta1Carsten Slotta2Peter Heimann3Michael Briese4Ulrich M. Weikert5Bita Massih6Silke Appenzeller7Silke Appenzeller8Michael Sendtner9Christian Kaltschmidt10Barbara Kaltschmidt11Barbara Kaltschmidt12Institute of Clinical Neurobiology, University Hospital Wuerzburg, Wuerzburg, GermanyDepartment of Cell Biology, University of Bielefeld, Bielefeld, GermanyMolecular Neurobiology, University of Bielefeld, Bielefeld, GermanyDepartment of Cell Biology, University of Bielefeld, Bielefeld, GermanyInstitute of Clinical Neurobiology, University Hospital Wuerzburg, Wuerzburg, GermanyDepartment of Cell Biology, University of Bielefeld, Bielefeld, GermanyInstitute of Clinical Neurobiology, University Hospital Wuerzburg, Wuerzburg, GermanyCore Unit Systems Medicine, University of Wuerzburg, Wuerzburg, GermanyComprehensive Cancer Center Mainfranken, University Hospital Wuerzburg, Wuerzburg, GermanyInstitute of Clinical Neurobiology, University Hospital Wuerzburg, Wuerzburg, GermanyDepartment of Cell Biology, University of Bielefeld, Bielefeld, GermanyDepartment of Cell Biology, University of Bielefeld, Bielefeld, GermanyMolecular Neurobiology, University of Bielefeld, Bielefeld, GermanyInflammation and dysregulation of the immune system are hallmarks of several neurodegenerative diseases. An activated immune response is considered to be the cause of myelin breakdown in demyelinating disorders. In the peripheral nervous system (PNS), myelin can be degraded in an autophagy-dependent manner directly by Schwann cells or by macrophages, which are modulated by T-lymphocytes. Here, we show that the NF-κB activator Pleckstrin homology containing family member 5 (Plekhg5) is involved in the regulation of both Schwann cell autophagy and recruitment of T-lymphocytes in peripheral nerves during motoneuron disease. Plekhg5-deficient mice show defective axon/Schwann cell units characterized by myelin infoldings in peripheral nerves. Even at late stages, Plekhg5-deficient mice do not show any signs of demyelination and inflammation. Using RNAseq, we identified a transcriptional signature for an impaired immune response in sciatic nerves, which manifested in a reduced number of CD4+ and CD8+ T-cells. These findings identify Plekhg5 as a promising target to impede myelin breakdown in demyelinating PNS disorders.https://www.frontiersin.org/article/10.3389/fncel.2020.00185/fullSchwann cellsautophagyimmune responsemyelinPLEKHG5 |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Patrick Lüningschrör Carsten Slotta Carsten Slotta Peter Heimann Michael Briese Ulrich M. Weikert Bita Massih Silke Appenzeller Silke Appenzeller Michael Sendtner Christian Kaltschmidt Barbara Kaltschmidt Barbara Kaltschmidt |
| spellingShingle |
Patrick Lüningschrör Carsten Slotta Carsten Slotta Peter Heimann Michael Briese Ulrich M. Weikert Bita Massih Silke Appenzeller Silke Appenzeller Michael Sendtner Christian Kaltschmidt Barbara Kaltschmidt Barbara Kaltschmidt Absence of Plekhg5 Results in Myelin Infoldings Corresponding to an Impaired Schwann Cell Autophagy, and a Reduced T-Cell Infiltration Into Peripheral Nerves Frontiers in Cellular Neuroscience Schwann cells autophagy immune response myelin PLEKHG5 |
| author_facet |
Patrick Lüningschrör Carsten Slotta Carsten Slotta Peter Heimann Michael Briese Ulrich M. Weikert Bita Massih Silke Appenzeller Silke Appenzeller Michael Sendtner Christian Kaltschmidt Barbara Kaltschmidt Barbara Kaltschmidt |
| author_sort |
Patrick Lüningschrör |
| title |
Absence of Plekhg5 Results in Myelin Infoldings Corresponding to an Impaired Schwann Cell Autophagy, and a Reduced T-Cell Infiltration Into Peripheral Nerves |
| title_short |
Absence of Plekhg5 Results in Myelin Infoldings Corresponding to an Impaired Schwann Cell Autophagy, and a Reduced T-Cell Infiltration Into Peripheral Nerves |
| title_full |
Absence of Plekhg5 Results in Myelin Infoldings Corresponding to an Impaired Schwann Cell Autophagy, and a Reduced T-Cell Infiltration Into Peripheral Nerves |
| title_fullStr |
Absence of Plekhg5 Results in Myelin Infoldings Corresponding to an Impaired Schwann Cell Autophagy, and a Reduced T-Cell Infiltration Into Peripheral Nerves |
| title_full_unstemmed |
Absence of Plekhg5 Results in Myelin Infoldings Corresponding to an Impaired Schwann Cell Autophagy, and a Reduced T-Cell Infiltration Into Peripheral Nerves |
| title_sort |
absence of plekhg5 results in myelin infoldings corresponding to an impaired schwann cell autophagy, and a reduced t-cell infiltration into peripheral nerves |
| publisher |
Frontiers Media S.A. |
| series |
Frontiers in Cellular Neuroscience |
| issn |
1662-5102 |
| publishDate |
2020-07-01 |
| description |
Inflammation and dysregulation of the immune system are hallmarks of several neurodegenerative diseases. An activated immune response is considered to be the cause of myelin breakdown in demyelinating disorders. In the peripheral nervous system (PNS), myelin can be degraded in an autophagy-dependent manner directly by Schwann cells or by macrophages, which are modulated by T-lymphocytes. Here, we show that the NF-κB activator Pleckstrin homology containing family member 5 (Plekhg5) is involved in the regulation of both Schwann cell autophagy and recruitment of T-lymphocytes in peripheral nerves during motoneuron disease. Plekhg5-deficient mice show defective axon/Schwann cell units characterized by myelin infoldings in peripheral nerves. Even at late stages, Plekhg5-deficient mice do not show any signs of demyelination and inflammation. Using RNAseq, we identified a transcriptional signature for an impaired immune response in sciatic nerves, which manifested in a reduced number of CD4+ and CD8+ T-cells. These findings identify Plekhg5 as a promising target to impede myelin breakdown in demyelinating PNS disorders. |
| topic |
Schwann cells autophagy immune response myelin PLEKHG5 |
| url |
https://www.frontiersin.org/article/10.3389/fncel.2020.00185/full |
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