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

Author

Listed:
  • Stefano Garofalo

    (Sapienza University of Rome)

  • Germana Cocozza

    (IRCCS Neuromed)

  • Alessandra Porzia

    (Sapienza University of Rome)

  • Maurizio Inghilleri

    (Sapienza University)

  • Marcello Raspa

    (EMMA CNR)

  • Ferdinando Scavizzi

    (EMMA CNR)

  • Eleonora Aronica

    (Amsterdam UMC, University of Amsterdam, department of (Neuro)Pathology, Amsterdam Neuroscience, Meibergdreef 9)

  • Giovanni Bernardini

    (Sapienza University of Rome)

  • Ling Peng

    (Aix-Marseille Université, CNRS, Centre Interdisciplinaire de Nanoscience de Marseille, UMR 7325, «Equipe Labellisée Ligue Contre le Cancer»)

  • Richard M. Ransohoff

    (Third Rock Ventures)

  • Angela Santoni

    (IRCCS Neuromed
    Sapienza University of Rome)

  • Cristina Limatola

    (IRCCS Neuromed
    Sapienza University, Laboratory affiliated to Istituto Pasteur Italia)

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, hSOD1G93A, 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, TDP43A315T. NK cells are neurotoxic to hSOD1G93A 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 hSOD1G93A 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.

Suggested Citation

  • Stefano Garofalo & Germana Cocozza & Alessandra Porzia & Maurizio Inghilleri & Marcello Raspa & Ferdinando Scavizzi & Eleonora Aronica & Giovanni Bernardini & Ling Peng & Richard M. Ransohoff & Angela, 2020. "Natural killer cells modulate motor neuron-immune cell cross talk in models of Amyotrophic Lateral Sclerosis," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15644-8
    DOI: 10.1038/s41467-020-15644-8
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    Cited by:

    1. Stefano Garofalo & Germana Cocozza & Alessandro Mormino & Giovanni Bernardini & Eleonora Russo & Donald Ielpo & Diego Andolina & Rossella Ventura & Katiuscia Martinello & Massimiliano Renzi & Sergio F, 2023. "Natural killer cells and innate lymphoid cells 1 tune anxiety-like behavior and memory in mice via interferon-γ and acetylcholine," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. I-Na Lu & Phyllis Fung-Yi Cheung & Michael Heming & Christian Thomas & Giovanni Giglio & Markus Leo & Merve Erdemir & Timo Wirth & Simone König & Christine A. Dambietz & Christina B. Schroeter & Chris, 2024. "Cell-mediated cytotoxicity within CSF and brain parenchyma in spinal muscular atrophy unaltered by nusinersen treatment," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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