The biological relevance of adenosine deamination in immune activation

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DESCRIPTION (provided by applicant): Adenosine is a potent suppressive agent that protects the host from excessive tissue injury associated with strong inflammation. In tissue stress, including infections, adenosine production is elevated. The higher levels of adenosine signal through adenosine receptors to exert strong anti-inflammatory effects, and thus protect host cells. Under in vitro settings, this suppressive effect is evident in immune cells as well. Adenosine, therefore, has been thought as playing a role of "calming" the immune system in disease conditions. This popular notion, however, is in contrast with another basic observation that the immune system is most activated precisely under the same circumstances. In our preliminary in vitro assays we discovered that dendritic cells, the initiator of immune reactions, used adenosine deaminase to rapidly remove adenosine from their surroundings. We hypothesize that this enzymatic activity may isolate dendritic cells from the suppression of adenosine, rendering them fully functional in infections. We propose here a set of common and highly optimized immunological assays to test the validity of this hypothesis in vivo. The outcome of this study will pave the way for future explorations on the topic. This study deals with a new concept in immune regulation, and will have impact on vaccine development, autoimmune disease intervention and cancer immunotherapy.