A2BAR expression in non-immune cells plays an important role in the development of murine colitis

BackgroundAdenosine, an endogenous purine nucleoside, is involved in several physiological functions. We have previously shown that A2BAR plays a pro-inflammatory role during colitis.AimsOur goals were to determine if A2BAR expression was necessary on immune cells/non-immune cells during colitis and if A2BAR was a suitable target for treating intestinal inflammation.MethodsWild-type and A2BAR knockout mice were utilized in bone marrow transplants to explore the importance of immune/non-immune A2BAR expression during the development of colitis. Additionally, a T-cell transfer model of colitis was used in Rag1 knockout or A2BAR/RAG1 double knockout recipients. Finally, A2BAR small interfering RNA nanoparticles were administered to dextran sodium sulphate-treated mice.ResultsWild-type mice receiving wild-type or knockout bone marrow developed severe colitis after dextran sodium sulphate treatment, whereas colitis was significantly attenuated in knockout mice receiving wild-type or knockout bone marrow. Colitis induced in Rag1 knockout animals was attenuated in A2BAR/RAG1 double knockout recipients. Animals receiving nanoparticles exhibited attenuated parameters of colitis severity compared to mice receiving control nanoparticles.ConclusionsOur results suggest that A2BAR on non-immune cells plays an important role for the induction of colitis and targeting A2BAR expression during colitis may be useful for alleviating symptoms of intestinal inflammation.