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Natural killer cells modulate motor neuron-immune cell cross talk in models of Amyotrophic Lateral Sclerosis
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Natural killer cells modulate motor neuron-immune cell cross talk in models of Amyotrophic Lateral Sclerosis
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Journal Article
Natural killer cells modulate motor neuron-immune cell cross talk in models of Amyotrophic Lateral Sclerosis
2020
Overview
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.
Neuroimmune interactions are important in amyotrophic lateral sclerosis (ALS). Here the authors characterize the role of NK cells in mouse models of ALS, and in patient tissue.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/31
/ 13/51
/ 13/89
/ 14
/ 14/19
/ 38
/ 38/77
/ 96
/ Adult
/ Aged
/ Amyotrophic lateral sclerosis
/ Amyotrophic Lateral Sclerosis - immunology
/ Amyotrophic Lateral Sclerosis - metabolism
/ Amyotrophic Lateral Sclerosis - pathology
/ Animals
/ Female
/ Humanities and Social Sciences
/ Humans
/ Killer Cells, Natural - immunology
/ Killer Cells, Natural - metabolism
/ Ligands
/ Male
/ Mice
/ Monocyte chemoattractant protein 1
/ Natural Cytotoxicity Triggering Receptor 1 - genetics
/ Natural Cytotoxicity Triggering Receptor 1 - metabolism
/ Science
