title: Myeloid-derived suppressor cells limit the inflammation by promoting T lymphocyte apoptosis in the spinal cord of a murine model of multiple sclerosis.
abstract: Multiple Sclerosis (MS) is a demyelinating/inflammatory disease of the central nervous system. Relapsing-remitting MS is characterized by a relapsing phase with clinical symptoms and the production of inflammatory cell infiltrates, and a period of remission during which patients recover partially. Myeloid-derived suppressor cells (MDSCs) are immature cells capable of suppressing the inflammatory response through Arginase-I (Arg-I) activity, among other mechanisms. Here, we have identified Arg-I(+) -MDSCs in the spinal cord during experimental autoimmune encephalomyelitis (EAE), cells that were largely restricted to the demyelinating plaque and that always exhibited the characteristic MDSC surface markers Arg-I/CD11b/Gr-1/M-CSF1R. The presence and density of Arg-I(+) -cells, and the proportion of apoptotic but not proliferative T cells, were correlated with the EAE time course: peaked in parallel with the clinical score, decreased significantly during the remitting phase and completely disappeared during the chronic phase. Spinal cord-isolated MDSCs of EAE animals augmented the cell death when co-cultured with stimulated control splenic CD3 T cells. These data point to an important role for MDSCs in limiting inflammatory damage in MS, favoring the relative recovery in the remitting phase of the disease. Thus, the MDSC population should be considered as a potential therapeutic target to accelerate the recovery of MS patients.
authors.affiliation: Grupo de Neurobiología del Desarrollo-GNDe, Hospital Nacional de Parapléjicos, Finca "La Peraleda" s/n, Toledo, Spain.
authors.forename: Verónica
authors.initials: V
authors.lastname: Moliné-Velázquez
authors.forename: Henar
authors.initials: H
authors.lastname: Cuervo
authors.forename: Virginia
authors.initials: V
authors.lastname: Vila-Del Sol
authors.forename: María Cristina
authors.initials: MC
authors.lastname: Ortega
authors.forename: Diego
authors.initials: D
authors.lastname: Clemente
authors.forename: Fernando
authors.initials: F
authors.lastname: de Castro
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001119:Arginase / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D005260:Female; D007108:Immune Tolerance / Q000276:immunology*; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000276:immunology / Q000473:pathology; D022423:Myeloid Cells / Q000166:cytology / Q000276:immunology*; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology*
chemical_list: C544448:Arg1 protein, mouse; D001119:Arginase