June 2, 2012
View Full PaperImmunoregulation through extracellular nucleotides
Key Result
Chronic stimulation with micromolar extracellular ATP inhibits T and NK lymphocyte proliferation and enhances dendritic cell tolerance, with significant differences between murine and human models.
Structured PICO
P
Population
Murine models and human immune cells (T and NK lymphocytes, dendritic cells) in the context of chronic inflammation and autoimmune diseases
I
Intervention
Extracellular ATP (eATP) stimulation
O
Outcome
Immune response regulation (proliferation of T and NK lymphocytes, dendritic cell tolerance)
The immunoregulatory role of eATP is complex and differs between mice and humans, which must be considered when evaluating its role in human inflammatory and autoimmune diseases.
Limitations
- Differences in P2 receptor expression between mice and humans are often overlooked when evaluating eATP in human diseases.
Abstract
Extracellular ATP (eATP), the most abundant among nucleotides, can act as a mediator during inflammatory responses by binding to plasmamembrane P2 purinergic receptors, which are widely expressed on cells of the immune system. eATP is generally considered as a classical danger signal, which stimulates immune responses in the presence of tissue damage. Converging evidence from several studies using murine models of chronic inflammation have supported this hypothesis; however, the role of eATP in the regulation of human immune function appears to be more complex. Chronic stimulation with micromolar eATP concentrations inhibits the proliferation of T and NK lymphocytes and enhances the capacity of dendritic cells to promote tolerance. The effect of eATP depends on multiple factors, such as the extent of stimulation, eATP concentration, presence/absence of other mediators in the microenvironment, and pattern of P2 receptor engagement. Small but significant differences in the pattern of P2 receptor expression in mice and humans confer the diverse capacities of ATP in regulating the immune response. Such diversity, which is often overlooked, should therefore be carefully considered when evaluating the role of eATP in human inflammatory and autoimmune diseases.