Caffeine and Multiple Sclerosis: Is protection in your coffee cup?

Abstract

The formation of extracellular adenosine during an inflammatory response serves as an immunosuppressive negative‐feedback signal to prevent excessive inflammation. Since CD73 is a cell surface enzyme that catalyzes the breakdown of AMP into adenosine, we investigated the role of CD73 (and extracellular adenosine) in controlling inflammation in experimental autoimmune encephalomyelitis (EAE), the animal model for the inflammatory autoimmune central nervous system (CNS) disease multiple sclerosis (MS). While we predicted that cd73−/− mice would develop severe EAE due to their inability to produce extracellular adenosine to modulate CNS inflammation, surprisingly, cd73−/− mice were resistant to EAE. In addition, cd73−/− mice had fewer CNS infiltrating lymphocytes compared to wild type mice following EAE induction. This EAE protection in cd73−/− mice cannot be attributed to a T cell functional deficiency since adoptively transferred CD4+ T cells from cd73−/− mice can potentiate severe EAE in tcrα −/− mice (which are normally resistant to EAE due to their lack of T cells). Moreover, while adenosine receptors (ARs) are expressed in the CNS, blockade of AR signaling with caffeine protects wild type mice from EAE development. Thus, we conclude that CD73 and AR signaling are required for the efficient entry of lymphocytes into the CNS during EAE, and quite possibly MS, development. AI 18220 (LFT) and AI 57854 (MSB)