The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
CNS Repair Requires Both Effector and Regulatory T Cells with Distinct Temporal and Spatial Profiles
Open accessAbstract
Monocyte-derived macrophages (mo-MΦs) and T cells have been shown to contribute to spinal cord repair. Recently, the remote brain choroid plexus epithelium (CP) was identified as a portal for monocyte recruitment, and its activation for leukocyte trafficking was found to be IFN-γ-dependent. Here, we addressed how the need for effector T cells can be reconciled with the role of inflammation-resolving immune cells in the repair process. Using an acute spinal cord injury model, we show that in mice deficient in IFN-γ-producing T cells, the CP was not activated, and recruitment of inflammation-resolving mo-MΦ to the spinal cord parenchyma was limited. We further demonstrate that mo-MΦ locally regulated recruitment of thymic-derived Foxp3(+) regulatory T (Treg) cells to the injured spinal cord parenchyma at the subacute/chronic phase. Importantly, an ablation protocol that resulted in reduced Tregs at this stage interfered with tissue remodeling, in contrast to Treg transient ablation, restricted to the 4 d period before the injury, which favored repair. The enhanced functional recovery observed following such a controlled decrease of Tregs suggests that reduced systemic immunosuppression at the time of the insult can enhance CNS repair. Overall, our data highlight a dynamic immune cell network needed for repair, acting in discrete compartments and stages, and involving effector and regulatory T cells, interconnected by mo-MΦ. Any of these populations may be detrimental to the repair process if their level or activity become dysregulated. Accordingly, therapeutic interventions must be both temporally and spatially controlled.
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Cites
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A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17
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Fibrotic disease and the TH1/TH2 paradigm
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T-bet: a bridge between innate and adaptive immunity
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“In addition, we observed lower numbers of NK and NK T cells, in line with the role of TBX21 in the development and maturation of NK cells (Townsend et al., 2004; Lazarevic et al., 2013); however, these cells represented minute populations at the injured spinal cord (1.”
BackgroundInfluentialIFN-γ-dependent activation of the brain’s choroid plexus for CNS immune surveillance and repair
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Self-citationFeatures of skin-coincubated macrophages that promote recovery from spinal cord injury
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Cited by
Regulatory T cells promote myelin regeneration in the central nervous system
Dombrowski, Y., O'Hagan, T., Dittmer, M., Penalva, R., Mayoral, S. R., Bankhead, P., Fleville, S., Eleftheriadis, G., Zhao, C., Naughton, M., et al. (2017) · Nature Neuroscience · doi:10.1038/nn.4528 · Cited by 533
Baruch, K., Rosenzweig, N., Kertser, A., Deczkowska, A., Sharif, A. M., Spinrad, A., Tsitsou-Kampeli, A., Sarel, A., Cahalon, L., & Schwartz, M. (2015) · Nature Communications · doi:10.1038/ncomms8967 · Cited by 491
Self-citationImmune cell regulation of glia during CNS injury and disease
Greenhalgh, A. D., David, S., & Bennett, F. C. (2020) · Nature Reviews Neuroscience · doi:10.1038/s41583-020-0263-9 · Cited by 396
Inflammatory neuroprotection following traumatic brain injury
Russo, M. V., & McGavern, D. B. (2016) · Science · doi:10.1126/science.aaf6260 · Cited by 375
Wattananit, S., Tornero, D., Graubardt, N., Memanishvili, T., Monni, E., Tatarishvili, J., Miskinyte, G., Ge, R., Ahlenius, H., Lindvall, O., et al. (2016) · The Journal of Neuroscience · doi:10.1523/jneurosci.4317-15.2016 · Cited by 353
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Metadata
- Authors
- Raposo, C., Graubardt, N., Cohen, M., Eitan, C., London, A., Berkutzki, T., & Schwartz, M.
- Venue
- Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2014-07-30
- Volume
- 34
- Issue
- 31
- Pages
- 10141-10155
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- OpenAlex
- W2049161101
- Cited by
- 161
- References
- 10
- FWCI
- 10.03
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Raposo, C., Graubardt, N., Cohen, M., Eitan, C., London, A., Berkutzki, T., & Schwartz, M. (2014). CNS Repair Requires Both Effector and Regulatory T Cells with Distinct Temporal and Spatial Profiles. Journal of Neuroscience. https://doi.org/10.1523/jneurosci.0076-14.2014
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
