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

Stefano Garofalo (), Germana Cocozza, Alessandra Porzia, Maurizio Inghilleri, Marcello Raspa, Ferdinando Scavizzi, Eleonora Aronica, Giovanni Bernardini, Ling Peng, Richard M. Ransohoff, Angela Santoni and Cristina Limatola ()
Additional contact information
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
Cristina Limatola: IRCCS Neuromed

Nature Communications, 2020, vol. 11, issue 1, 1-16

Abstract: 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.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41467-020-15644-8 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15644-8

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-15644-8

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().