Regarding adenosine metabolism, it has been observed in a humanized GvHD mouse model that MSC-EVs can transfer CD73 to CD39 enzyme on the surface of tissue-infiltrating Th1 cells, thus inducing a significant production of adenosine that eventually reduces CD39 expression, enhances apoptosis of adenosine A2A receptor-expressing Th1 cells, and downregulates IFN-γ and TNF-α expression, without inducing Tregs (Amarnath et al., 2015). This evidence concerns the gene TNF and graft versus host disease.