| Autor: |
Garofalo S; Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy. stefano.garofalo@uniroma1.it., Cocozza G; IRCCS Neuromed, Pozzilli, Italy., Porzia A; Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy., Inghilleri M; Department of Human Neuroscience, Sapienza University, Rome, Italy., Raspa M; EMMA CNR, Monterotondo, Italy., Scavizzi F; EMMA CNR, Monterotondo, Italy., Aronica E; Amsterdam UMC, University of Amsterdam, department of (Neuro)Pathology, Amsterdam Neuroscience, Meibergdreef 9, Amsterdam, The Netherlands., Bernardini G; Department of Molecular Medicine, laboratory affiliated to Istituto Pasteur Italia, Sapienza University of Rome, Rome, Italy., Peng L; Aix-Marseille Université, CNRS, Centre Interdisciplinaire de Nanoscience de Marseille, UMR 7325, «Equipe Labellisée Ligue Contre le Cancer», Marseille, France., Ransohoff RM; Third Rock Ventures, Boston, MA, USA., Santoni A; IRCCS Neuromed, Pozzilli, Italy.; Department of Molecular Medicine, laboratory affiliated to Istituto Pasteur Italia, Sapienza University of Rome, Rome, Italy., Limatola C; IRCCS Neuromed, Pozzilli, Italy. cristina.limatola@uniroma1.it.; Department of Physiology and Pharmacology, Sapienza University, Laboratory affiliated to Istituto Pasteur Italia, Rome, Italy. cristina.limatola@uniroma1.it. |
| Abstrakt: |
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. |
