TY  - JOUR
A1  - Groh, Janos
A1  - Abdelwahab, Tassnim
A1  - Kattimani, Yogita
A1  - Hörner, Michaela
A1  - Loserth, Silke
A1  - Gudi, Viktoria
A1  - Adalbert, Robert
A1  - Imdahl, Fabian
A1  - Saliba, Antoine-Emmanuel
A1  - Coleman, Michael
A1  - Stangel, Martin
A1  - Simons, Mikael
A1  - Martini, Rudolf
T1  - Microglia-mediated demyelination protects against CD8\(^+\) T cell-driven axon degeneration in mice carrying PLP defects
JF  - Nature Communications
N2  - Axon degeneration and functional decline in myelin diseases are often attributed to loss of myelin but their relation is not fully understood. Perturbed myelinating glia can instigate chronic neuroinflammation and contribute to demyelination and axonal damage. Here we study mice with distinct defects in the proteolipid protein 1 gene that develop axonal damage which is driven by cytotoxic T cells targeting myelinating oligodendrocytes. We show that persistent ensheathment with perturbed myelin poses a risk for axon degeneration, neuron loss, and behavioral decline. We demonstrate that CD8\(^+\) T cell-driven axonal damage is less likely to progress towards degeneration when axons are efficiently demyelinated by activated microglia. Mechanistically, we show that cytotoxic T cell effector molecules induce cytoskeletal alterations within myelinating glia and aberrant actomyosin constriction of axons at paranodal domains. Our study identifies detrimental axon-glia-immune interactions which promote neurodegeneration and possible therapeutic targets for disorders associated with myelin defects and neuroinflammation.
KW  - diseases of the nervous system
KW  - myelin biology and repair
KW  - neuroimmunology
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357641
VL  - 14
ER  -