Neuroinflammation by Cytotoxic T-Lymphocytes Impairs Retrograde Axonal Transport in an Oligodendrocyte Mutant Mouse
Please always quote using this URN: urn:nbn:de:bvb:20-opus-134982
- Mice overexpressing proteolipid protein (PLP) develop a leukodystrophy-like disease involving cytotoxic, CD8+ T-lymphocytes. Here we show that these cytotoxic T-lymphocytes perturb retrograde axonal transport. Using fluorogold stereotactically injected into the colliculus superior, we found that PLP overexpression in oligodendrocytes led to significantly reduced retrograde axonal transport in retina ganglion cell axons. We also observed an accumulation of mitochondria in the juxtaparanodal axonal swellings, indicative for a disturbed axonalMice overexpressing proteolipid protein (PLP) develop a leukodystrophy-like disease involving cytotoxic, CD8+ T-lymphocytes. Here we show that these cytotoxic T-lymphocytes perturb retrograde axonal transport. Using fluorogold stereotactically injected into the colliculus superior, we found that PLP overexpression in oligodendrocytes led to significantly reduced retrograde axonal transport in retina ganglion cell axons. We also observed an accumulation of mitochondria in the juxtaparanodal axonal swellings, indicative for a disturbed axonal transport. PLP overexpression in the absence of T-lymphocytes rescued retrograde axonal transport defects and abolished axonal swellings. Bone marrow transfer from wildtype mice, but not from perforin- or granzyme B-deficient mutants, into lymphocyte-deficient PLP mutant mice led again to impaired axonal transport and the formation of axonal swellings, which are predominantly located at the juxtaparanodal region. This demonstrates that the adaptive immune system, including cytotoxic T-lymphocytes which release perforin and granzyme B, are necessary to perturb axonal integrity in the PLP-transgenic disease model. Based on our observations, so far not attended molecular and cellular players belonging to the immune system should be considered to understand pathogenesis in inherited myelin disorders with progressive axonal damage.…
Author: | Chi Wang Ip, Antje Kroner, Janos Groh, Marianne Huber, Dennis Klein, Irene Spahn, Ricarda Diem, Sarah K. Williams, Klaus-Armin Nave, Julia M. Edgar, Rudolf Martini |
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URN: | urn:nbn:de:bvb:20-opus-134982 |
Document Type: | Journal article |
Faculties: | Medizinische Fakultät / Neurologische Klinik und Poliklinik |
Language: | English |
Parent Title (English): | PLoS One |
Year of Completion: | 2012 |
Volume: | 7 |
Issue: | 8 |
Pagenumber: | e42554 |
Source: | PLoS ONE 7(8): e42554. doi:10.1371/journal.pone.0042554 |
DOI: | https://doi.org/10.1371/journal.pone.0042554 |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 616 Krankheiten |
Tag: | axonopathic changes; degeneration; experimental autoimmune encephalomyelitis; granzyme B; motor function; multiple sclerosis; myelin; nervous system; neural apoptosis; proteolipid protein gene; retinal ganglion cells |
Release Date: | 2017/12/17 |
Licence (German): | CC BY: Creative-Commons-Lizenz: Namensnennung |