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Garofalo, Stefano; Cocozza, Germana; Porzia, Alessandra; Inghilleri, Maurizio; Raspa, Marcello; Scavizzi, Ferdinando; Aronica, Eleonora; Bernardini, Giovanni; Peng, Ling; Ransohoff, Richard M; Santoni, Angela; Limatola, Cristina
Nature communications, 04/2020, Letnik: 11, Številka: 1Journal Article
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 , 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 . NK cells are neurotoxic to hSOD1 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 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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