The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
CD4+ T cells support glial neuroprotection, slow disease progression, and modify glial morphology in an animal model of inherited ALS
Open accessAbstract
Neuroinflammation, marked by gliosis and infiltrating T cells, is a prominent pathological feature in diverse models of dominantly inherited neurodegenerative diseases. Recent evidence derived from transgenic mice ubiquitously overexpressing mutant Cu 2+ /Zn 2+ superoxide dismutase (mSOD1), a chronic neurodegenerative model of inherited amyotrophic lateral sclerosis (ALS), indicates that glia with either a lack of or reduction in mSOD1 expression enhance motoneuron protection and slow disease progression. However, the contribution of T cells that are present at sites of motoneuron injury in mSOD1 transgenic mice is not known. Here we show that when mSOD1 mice were bred with mice lacking functional T cells or CD4+ T cells, motoneuron disease was accelerated, accompanied by unexpected attenuated morphological markers of gliosis, increased mRNA levels for proinflammatory cytokines and NOX2, and decreased levels of trophic factors and glial glutamate transporters. Bone marrow transplants reconstituted mice with T cells, prolonged survival, suppressed cytotoxicity, and restored glial activation. These results demonstrate for the first time in a model of chronic neurodegeneration that morphological activation of microglia and astroglia does not predict glial function, and that the presence of CD4+ T cells provides supportive neuroprotection by modulating the trophic/cytotoxic balance of glia. These glial/T-cell interactions establish a novel target for therapeutic intervention in ALS and possibly other neurodegenerative diseases.
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Onset and Progression in Inherited ALS Determined by Motor Neurons and Microglia
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Cited by
Mechanisms underlying inflammation in neurodegeneration
Glass, C. K., Saijo, K., Winner, B., Marchetto, M. C., & Gage, F. H. (2010) · Cell · doi:10.1016/j.cell.2010.02.016 · Cited by 3,580
Differential Roles of M1 and M2 Microglia in Neurodegenerative Diseases
Tang, Y., & Le, W. (2016) · Molecular Neurobiology · doi:10.1007/s12035-014-9070-5 · Cited by 2,190
Microglia states and nomenclature: A field at its crossroads
Paolicelli, R. C., Sierra, A., Stevens, B., Tremblay, M.-E., Aguzzi, A., Ajami, B., Amit, I., Audinat, E., Bechmann, I., Bennett, M., et al. (2022) · Neuron · doi:10.1016/j.neuron.2022.10.020 · Cited by 1,973
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Ilieva, H., Polymenidou, M., & Cleveland, D. W. (2009) · Journal of Cell Biology · doi:10.1083/jcb.200908164 · Cited by 1,008
Metadata
- Authors
- Beers, D. R., Henkel, J. S., Zhao, W., Wang, J., & Appel, S. H.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2008-10-07
- Volume
- 105
- Issue
- 40
- Pages
- 15558-15563
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2123848058
- Cited by
- 466
- References
- 34
- FWCI
- 17.09
- Type
- journal article
- Language
- en
- Open access
- green
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- Beers, D. R., Henkel, J. S., Zhao, W., Wang, J., & Appel, S. H. (2008). CD4+ T cells support glial neuroprotection, slow disease progression, and modify glial morphology in an animal model of inherited ALS. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0807419105
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