Adenosine deaminase ADAR2 modulates immune T cell functions Deamination of adenosine to inosine (A-to-I) is the most abundant form of RNA editing in mammalian cells and are catalyzed by adenosine deaminases (ADARs). RNA editing contributes to homeostatic innate immune and neurological functions, as well as pathologies in cancers. However, the upstream molecular mechanisms regulating this pathway remained to be elucidated. Here, we report that the Adarb1 locus encoding ADAR2 is significantly upregulated during adaptive immune T helper cell activation and polarization toward the T helper 17 (Th17) lineage. Mechanistically, transcription factor IRF4 together with the establishment of an intragenic super enhancer turns on Adarb1 transcription. Post-transcriptionally, Adarb1 transcripts were bound and regulated by RNA binding protein DDX5. Knocking out DDX5 dampens ADAR2 expression and reduced global RNA editing, resulting in dysregulated expression of HIF1α and loss of effector function in Th17 cells.