Interestingly, in the air pouch model, an in vivo model that mimics the synovial cavity, we have also demonstrated that the anti-inflammatory actions of MTX, the cornerstone treatment for rheumatoid arthritis, are mediated in large part, by increasing adenosine levels [17], which, via activation of the A2AR, increase intracellular cAMP levels [21]. Here, ADORA2A is linked to rheumatoid arthritis.