Intain a long-term Foxp3 expression and suppressive activity, and since they

The impact of extracellular ATP on the immune system is critical since its increase induces the activation of the inflammosome and subsequent release of cytokines, such as IL-1 (68, 69), in response to damage-associated molecular patterns (DAMPS) and pathogen-associated molecular patterns (PAMPS) (70). Therefore, extracellular ATP is considered a danger signal liberated by damaged or dying cells that induces pro- and anti-inflammatory signals. In the context of immune chronic activation as in HIV infection, ATP released by activated T cells seems to have an autocrine effect, prolonging activation and IL-2 secretion (71). In contrast to ATP, adenosine exhibits anti-proliferative and inhibitory effects, hence giving to the CD39/CD73 activity an immune suppressive role (10). In fact, it was shown that induced title= 1940-0640-8-15 Treg expressing CD39+ acquired E7389 mesylate higher suppressive capacity than CD39neg iTreg (72). Adenosine plays an antagonistic role on Treg compared to non-Treg responses by directly binding to the adenosine 2a receptor (A2AR), consequently inducing the adenylyl cyclase activity and, therefore, increasing the intracellular cAMP level. ATP removal and A2AR activation elicits inhibitory functions in dendritic cells and activated T-cell subsets, inducing T-cell anergy (73); whereas in Treg, A2AR induces the generation of Foxp3+ Tregs (73) and enhances Treg immunosuppressive mechanisms (74, 75). Summing up, Treg could dampen immune activation as well as order ENMD-2076 induce activated T-cell dysfunction through CD39/CD73 activity. It is interesting to note that a study of CD39/CD73 distribution in Treg and conventional CD4+ T cells showed that even though CD39 is largely expressed on human Treg (CD4+ CD25hiFoxp3+ T cells), CD73 is not so widely expressed and title= rstb.2013.0181 responses, metabolic stress, or other types of cell injury.