Natural killer cells modulate motor neuron-immune cell cross talk in models of Amyotrophic Lateral Sclerosis
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In amyotrophic lateral sclerosis (ALS), immune cells and glia contribute to motor neuron (MN) degeneration. We report the presence of NK cells in post-mortem ALS motor cortex and spinal cord tissues, and the expression of NKG2D ligands on MNs. Using a mouse model of familial-ALS, hSOD1 G93A , we demonstrate NK cell accumulation in the motor cortex and spinal cord, with an early CCL2-dependent peak. NK cell depletion reduces the pace of MN degeneration, delays motor impairment and increases survival. This is confirmed in another ALS mouse model, TDP43 A315T . NK cells are neurotoxic to hSOD1 G93A MNs which express NKG2D ligands, while IFNγ produced by NK cells instructs microglia toward an inflammatory phenotype, and impairs FOXP3 + /Treg cell infiltration in the spinal cord of hSOD1 G93A mice. Together, these data suggest a role of NK cells in determining the onset and progression of MN degeneration in ALS, and in modulating Treg recruitment and microglia phenotype.
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NK cell infiltration into the spinal cord and cerebral motor cortex was observed in sporadic ALS patients and an ALS mouse model (SOD1G93A).
“NK cell infiltration into the spinal cord and cerebral motor cortex was observed in sporadic ALS patients and an ALS mouse model (SOD1G93A).”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [365]
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- Authors
- Garofalo, S., Cocozza, G., Porzia, A., Inghilleri, M., Raspa, M., Scavizzi, F., Aronica, E., Bernardini, G., Peng, L., Ransohoff, R. M., Santoni, A., & Limatola, C.
- Affiliations
- Sapienza University of Rome (IT)
- Istituto Neurologico Mediterraneo (IT)
- Institute of Cell Biology and Neurobiology (IT)
- Netherlands Institute for Neuroscience (NL)
- Istituto Pasteur (IT)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Garofalo, Stefano
- Limatola, Cristina
- ORCID
- Venue
- Nature Communications
- Published
- 2020-04-14
- Volume
- 11
- Issue
- 1
- Pages
- 1773-1773
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC7156729
- OpenAlex
- W3015391013
- Cited by
- 170
- References
- 50
- Citations by year
- 2026: 24 · 2025: 25 · 2024: 30 · 2023: 36 · 2022: 25 · 2021: 19 · 2020: 11
- FWCI
- 9.85
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, cc-by)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, cc-by)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- HAL (submittedVersion, cc-by)
- HAL (submittedVersion, other-oa)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Agence Nationale de la Recherche (ANR-16-ENM2-0004)
- Ministero dell’Istruzione, dell’Università e della Ricerca (PRIN 2015, H2020)
- Associazione Italiana per la Ricerca sul Cancro (PRIN 2015)
- Fondazione Italiana per la Ricerca sul Cancro (22329)
- Horizon 2020 Framework Programme
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
- Keywords
- amyotrophic lateral sclerosis, natural killer cells, motor neuron degeneration, NKG2D ligands, MCP-1, microglial activation, interferon-gamma, regulatory T cells, neuroinflammation, motor cortex, spinal cord, neurotoxicity
- MeSH terms
- Adult, Aged, Amyotrophic Lateral Sclerosis, Animals, Disease Models, Animal, Female, Humans, Killer Cells, Natural, Male, Middle Aged, Motor Cortex, Motor Neurons, Spinal Cord, Disease Progression, Mice, Natural Cytotoxicity Triggering Receptor 1
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