Cited by 170Amyotrophic Lateral Sclerosis ResearchNeuroinflammation and Neurodegeneration MechanismsImmune Cell Function and Interaction

Natural killer cells modulate motor neuron-immune cell cross talk in models of Amyotrophic Lateral Sclerosis

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Garofalo, Stefano, Cocozza, Germana, Porzia, Alessandra, Inghilleri, Maurizio, Raspa, Marcello, Scavizzi, Ferdinando, Aronica, Eleonora, Bernardini, Giovanni +4 more·2020·Nature Communications

Abstract

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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Crossref · 10.1038/s41467-020-15644-8

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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).”

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  1. [45]Ludolph A Amyotrophic lateral sclerosis & frontotemporal degeneration A Revis. El Escorial criteria 2015 16 291 292 26121170

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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
Venue
Nature Communications
Published
2020-04-14
Volume
11
Issue
1
Pages
1773-1773
ISSN
2041-1723 (ISSN-L)
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
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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