Proposed model for the beneficial role of AP, CD73 and CD39 in the generation of autoreactive T cells and subsequent neuroinflammation. AP detoxifies LPS derived from the gut microbiota or from the adjuvant in the case of EAE. During activation of T cells in the peripheral lymph nodes (LN) ATP is generated. CD73 and CD39, expressed on regulatory T cells, may reduce the high ATP concentration, which serves as an immunological danger signal. CD39 and AP convert ATP into ADP and AMP, whereas CD73 and AP convert AMP into the immunosuppressive adenosine. In the CNS, CD39 and CD73 are present on the endothelium and the glia limitans, respectively, where they may also reduce extracellular ATP levels. Within the lesion, stressed oligodendrocytes release ATP, which can be converted by CD39 upregulated on activated microglia. AP, alkaline phosphatase; CNS, central nervous system; EAE, experimental autoimmune encephalomyelitis; LPS, lipopolysaccharide.