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.
Natural killer cells modulate motor neuron-immune cell cross talk in models of amyotrophic lateral sclerosis / Garofalo, Stefano; Cocozza, Germana; Porzia, Alessandra; Inghilleri, Maurizio; Raspa, Marcello; Scavizzi, Ferdinando; Aronica, Eleonora; Bernardini, Giovanni; Peng, Ling; M Ransohoff, Richard; Santoni, Angela; Limatola, Cristina. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 1:11(2020). [10.1038/s41467-020-15644-8]
Natural killer cells modulate motor neuron-immune cell cross talk in models of amyotrophic lateral sclerosis
Stefano Garofalo
Primo
Conceptualization
;Germana CocozzaSecondo
Methodology
;Alessandra PorziaInvestigation
;Maurizio InghilleriResources
;Marcello RaspaResources
;Eleonora AronicaResources
;Giovanni BernardiniFormal Analysis
;Angela SantoniPenultimo
Supervision
;Cristina Limatola
Ultimo
Project Administration
2020
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.File | Dimensione | Formato | |
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