Figure 2
Figure 2. Diverse regulation of leukocyte function exerted by ATP. ATP can exert different effects on immune cells depending on which receptor is engaged. On DCs, ATP induces inflammasome activation and secretion of proinflammatory cytokines on binding to P2X7, whereas the activation of P2Y11 leads to a reduced production of proinflammatory cytokines and chemokines (in the presence of lipopolysaccharide) and to the production of immunosuppressive molecules, such as indoleamine 2,3-dioxygenase (IDO) and thrombospondin-1. On the other hand, in the presence of TNF-α, the secretion of IL-12 from DCs is increased. Activation of P2X7 on effector T lymphocytes increases IL-2 secretion and proliferation; in contrast, binding of P2Y11 determines a reduction in INF-γ and IL-2 production and limits proliferation. ATP has a crucial role in maintaining the homeostasis of regulatory T cells, as these lymphocytes are particularly sensitive to apoptosis induced by P2X7 activation. The effects of P2Y11 activation on Tregs are currently not known. ATP reduces IFN-γ production, proliferation, and cytotoxic activity in NK cells through the activation of P2Y11, whereas the engagement of P2X7 leads to cell death.

Diverse regulation of leukocyte function exerted by ATP. ATP can exert different effects on immune cells depending on which receptor is engaged. On DCs, ATP induces inflammasome activation and secretion of proinflammatory cytokines on binding to P2X7, whereas the activation of P2Y11 leads to a reduced production of proinflammatory cytokines and chemokines (in the presence of lipopolysaccharide) and to the production of immunosuppressive molecules, such as indoleamine 2,3-dioxygenase (IDO) and thrombospondin-1. On the other hand, in the presence of TNF-α, the secretion of IL-12 from DCs is increased. Activation of P2X7 on effector T lymphocytes increases IL-2 secretion and proliferation; in contrast, binding of P2Y11 determines a reduction in INF-γ and IL-2 production and limits proliferation. ATP has a crucial role in maintaining the homeostasis of regulatory T cells, as these lymphocytes are particularly sensitive to apoptosis induced by P2X7 activation. The effects of P2Y11 activation on Tregs are currently not known. ATP reduces IFN-γ production, proliferation, and cytotoxic activity in NK cells through the activation of P2Y11, whereas the engagement of P2X7 leads to cell death.

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