A1 and A2A adenosine receptors play a protective role to reduce prevalence of autoimmunity following tissue damage

Abstract

Adenosine is a potent modulator that has a tremendous effect on the immune system.Adenosine affects T cell activity, and is necessary in maintaining the T helper/regulatory T cell (T reg ) ratio. Adenosine signalling is also involved in activating neutrophils and the formation of neutrophil extracellular traps (NETs), which has been linked to autoimmune disorders. Therefore, adenosine, through its receptors, is extremely important in maintaining homeostasis and involved in the development of autoimmune diseases. In this study, we aim to evaluate the role of adenosine A 1 and A 2A receptors in involvement of autoimmune diseases. We studied adenosine regulation by NETosis in vitro, and used two murine models of autoimmune diseases: type I diabetes mellitus (T1DM) induced by low-dose streptozotocin and pristane-induced systemic lupus erythematosus (SLE). We have found that A 1 R enhances and A 2A R suppresses NETosis. In addition, in both models, A 1 R-knock-out (KO) mice were predisposed to the development of autoimmunity.In the SLE model in wild-type (WT) mice we observed a decline of A 1 R mRNA levels 6 h after pristane injection that was parallel to lymphocyte reduction. Following pristane,

Role of adenosine A2a receptor in cancers and autoimmune diseases

“… 63 A2AR can suppress NETosis in a low‐dose streptozotocin‐induced T1DM model, and plays a protective role in reducing tissue damage. 83 A2AR gene variants have also been shown to be protective against retinopathy in type 1 diabetes. 84 …”

“…63 A2AR can suppress NETosis in a low-dose streptozotocin-induced T1DM model, and plays a protective role in reducing tissue damage. 83 A2AR gene variants have also been shown to be protective against retinopathy in type 1 diabetes. 84 Multiple sclerosis (MS) is a chronic autoimmune disease involving the central nervous system, and experimental autoimmune encephalomyelitis (EAE) is the most widely used research model of MS. 85 Consistent roles of A2AR appear in the EAE models.…”

“…A2AR expression was significantly increased in coronary smooth muscle and endothelial cells in a mouse model of type 1 diabetes mellitus (T1DM), and activation of A2AR plays key role in the regulation of coronary blood flow 63 . A2AR can suppress NETosis in a low‐dose streptozotocin‐induced T1DM model, and plays a protective role in reducing tissue damage 83 . A2AR gene variants have also been shown to be protective against retinopathy in type 1 diabetes 84 …”

Role of the Sympathetic Nervous System in Mild Chronic Inflammatory Diseases: Focus on Osteoarthritis

“…Neutrophils are also able to produce adenosine by converting released ATP [84,85]. Activation of A1aR promotes chemotaxis, whereas A2A-and A2BaRs suppress neutrophil activation [86]. Especially Sympathetic Nervous System and Mild Chronic Inflammation targeting the A2AaR resulted in decreased IL-8 release by neutrophils [87].…”

Adenosine and Inflammation: Here, There and Everywhere

“…Studies have demonstrated that all four AR subtypes are expressed in neutrophils [25]. In particular, A 1 ARs promote neutrophil chemotaxis, whereas A 2A and A 2B ARs inhibit neutrophil activation [32]. In fact, treatment with the A 2A AR agonist, ATL313, inhibits critical steps in integrin-dependent neutrophil adhesion in vitro and in vivo [33].…”