Molecular neurodegeneration, 2018-08, Vol.13 (1), p.42-42, Article 42
2018
Details
- Autor(en) / Beteiligte
- Titel
- Counteracting roles of MHCI and CD8+ T cells in the peripheral and central nervous system of ALS SOD1G93A mice
- Ist Teil von
- Molecular neurodegeneration, 2018-08, Vol.13 (1), p.42-42, Article 42
- Ort / Verlag
- London: BioMed Central Ltd
- Erscheinungsjahr
- 2018
- Link zum Volltext
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Background The major histocompatibility complex I (MHCI) is a key molecule for the interaction of mononucleated cells with CD8.sup.+T lymphocytes. We previously showed that MHCI is upregulated in the spinal cord microglia and motor axons of transgenic SOD1.sup.G93A mice. Methods To assess the role of MHCI in the disease, we examined transgenic SOD1.sup.G93A mice crossbred with [beta]2 microglobulin-deficient mice, which express little if any MHCI on the cell surface and are defective for CD8.sup.+ T cells. Results The lack of MHCI and CD8.sup.+ T cells in the sciatic nerve affects the motor axon stability, anticipating the muscle atrophy and the disease onset. In contrast, MHCI depletion in resident microglia and the lack of CD8.sup.+ T cell infiltration in the spinal cord protect the cervical motor neurons delaying the paralysis of forelimbs and prolonging the survival of SOD1.sup.G93A mice. Conclusions We provided straightforward evidence for a dual role of MHCI in the peripheral nervous system (PNS) compared to the CNS, pointing out regional and temporal differences in the clinical responses of ALS mice. These findings offer a possible explanation for the failure of systemic immunomodulatory treatments and suggest new potential strategies to prevent the progression of ALS. Keywords: Amyotrophic lateral sclerosis, SOD1G93A mice, Neuroinflammation, MHCI, CD8+ T cells, Motor neuron, Peripheral nervous system
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1750-1326eISSN: 1750-1326DOI: 10.1186/s13024-018-0271-7Titel-ID: cdi_doaj_primary_oai_doaj_org_article_74ee0539682b47d6a3aaab1de9688c97
- Format
- –
- Schlagworte
- Amyotrophic lateral sclerosis, Antigens, Atrophy, Axons, Care and treatment, CD8 antigen, CD8+ T cells, Cell surface, Cell survival, Central nervous system, Development and progression, Health aspects, Immunity, Immunomodulation, Lymphocytes, Lymphocytes T, Major histocompatibility complex, MHCI, Microglia, Motor neuron, Motor neurons, Mutation, Nerves, Peripheral, Nervous system, Neuroinflammation, Paralysis, Pathology, Prevention, Sciatic nerve, SOD1G93A mice, Spinal cord, T cells, Transgenic mice