Excess circulating alternatively activated myeloid (M2) cells accelerate ALS progression while inhibiting experimental autoimmune encephalomyelitis.

Background: Circulating immune cells including autoreactive T cells and monocytes have been documented as key players in maintaining, protecting and repairing the central nervous system (CNS) in health and disease. Here, we hypothesized that neurodegenerative diseases might be associated, similarly to tumors, with increased levels of circulating peripheral myeloid derived suppressor cells (MDSCs), representing a subset of suppressor cells that often expand under pathological conditions and inhibit possible recruitment of helper T cells needed for fighting off the disease.

Methods And Findings: We tested this working hypothesis in amyotrophic lateral sclerosis (ALS) and its mouse model, which are characterized by a rapid progression once clinical symptoms are evident.

Application of glatiramer acetate to neurodegenerative diseases beyond multiple sclerosis: the need for disease-specific approaches.

Adaptive and innate immunity, if well controlled, contribute to the maintenance of the CNS, as well as to downregulation of adverse acute and chronic neurological conditions. T cells that recognize CNS antigens are needed to activate resident immune cells and to recruit blood-borne monocytes, which act to restore homeostasis and facilitate repair. However, boosting such a T-cell response in a risk-free way requires a careful choice of the antigen, carrier, and regimen.

Microglia can be induced by IFN-gamma or IL-4 to express neural or dendritic-like markers.

Microglia are resident cells in the central nervous system (CNS), of hematopoietic origin with a high plasticity. In this study, we examined whether adaptive immune system, involving in CNS maintenance and repair, can induce microglia to express markers of neural cells. We show that long exposure (above 10 days) of microglia to low doses (10 ng/ml) of the 'proinflammatory' T-cell derived cytokine, IFN-gamma, induced them to express neuronal markers including gamma-aminobutyric acid (GABA) and glutamic acid decarboxylase (GAD-67).