%0 Journal Article %1 Abdelwahab_2023 %A Abdelwahab, Tassnim %A Stadler, David %A Knöpper, Konrad %A Arampatzi, Panagiota %A Saliba, Antoine-Emmanuel %A Kastenmüller, Wolfgang %A Martini, Rudolf %A Groh, Janos %D 2023 %I Elsevier BV %J iScience %K myown %N 5 %P 106698 %R 10.1016/j.isci.2023.106698 %T Cytotoxic CNS-associated Tcells drive axon degeneration by targeting perturbed oligodendrocytes in PLP1 mutant mice %U https://doi.org/10.1016%2Fj.isci.2023.106698 %V 26 %X Myelin defects lead to neurological dysfunction in various diseases and in normal aging. Chronic neuroinflammation often contributes to axon-myelin damage in these conditions and can be initiated and/or sustained by perturbed myelinating glia. We have previously shown that distinct PLP1 mutations result in neurodegeneration that is largely driven by adaptive immune cells. Here we characterize CD8+ CNS-associated T cells in myelin mutants using single-cell transcriptomics and identify population heterogeneity and disease-associated changes. We demonstrate that early sphingosine-1-phosphate receptor modulation attenuates T cell recruitment and neural damage, while later targeting of CNS-associated T cell populations is inefficient. Applying bone marrow chimerism and utilizing random X chromosome inactivation, we provide evidence that axonal damage is driven by cytotoxic, antigen specific CD8+ T cells that target mutant myelinating oligodendrocytes. These findings offer insights into neural-immune interactions and are of translational relevance for neurological conditions associated with myelin defects and neuroinflammation.

@article{Abdelwahab_2023, abstract = {Myelin defects lead to neurological dysfunction in various diseases and in normal aging. Chronic neuroinflammation often contributes to axon-myelin damage in these conditions and can be initiated and/or sustained by perturbed myelinating glia. We have previously shown that distinct PLP1 mutations result in neurodegeneration that is largely driven by adaptive immune cells. Here we characterize CD8+ CNS-associated T cells in myelin mutants using single-cell transcriptomics and identify population heterogeneity and disease-associated changes. We demonstrate that early sphingosine-1-phosphate receptor modulation attenuates T cell recruitment and neural damage, while later targeting of CNS-associated T cell populations is inefficient. Applying bone marrow chimerism and utilizing random X chromosome inactivation, we provide evidence that axonal damage is driven by cytotoxic, antigen specific CD8+ T cells that target mutant myelinating oligodendrocytes. These findings offer insights into neural-immune interactions and are of translational relevance for neurological conditions associated with myelin defects and neuroinflammation.}, added-at = {2023-06-09T14:04:25.000+0200}, author = {Abdelwahab, Tassnim and Stadler, David and Knöpper, Konrad and Arampatzi, Panagiota and Saliba, Antoine-Emmanuel and Kastenmüller, Wolfgang and Martini, Rudolf and Groh, Janos}, biburl = {https://www.bibsonomy.org/bibtex/233aa03d590424bbf76b663186621b04f/cusysmed}, day = 19, doi = {10.1016/j.isci.2023.106698}, interhash = {032a0bf50ef30489197084976867262e}, intrahash = {33aa03d590424bbf76b663186621b04f}, journal = {iScience}, keywords = {myown}, month = may, number = 5, pages = 106698, publisher = {Elsevier BV}, timestamp = {2024-04-16T15:57:27.000+0200}, title = {Cytotoxic CNS-associated Tcells drive axon degeneration by targeting perturbed oligodendrocytes in PLP1 mutant mice}, url = {https://doi.org/10.1016%2Fj.isci.2023.106698}, volume = 26, year = 2023 }