RNA editing enzyme ADAR1 is required for early T cell development

Abstract The RNA editing enzyme ADAR1 has been shown to be an essential molecule for hematopoietic cell differentiation, embryonic development, and regulation of immune responses. Here, we present evidence in a T-cell-specific gene knockout mouse model that ADAR1 is required for early T cell development. Loss of ADAR1 led to cell death of the progenitors at the double negative stage and prevented T cell maturation in the thymus. Furthermore, ADAR1 deletion in pre-T cells preferentially affected TCRβ-expressing cells causing TCRβ positive cell depletion. Interruption of IFN signaling occurred in the premature T cells, indicating a role of IFN signaling in the survival of TCRβ-expressing cells regulated by ADAR1. This study demonstrated an essential role for the RNA editing enzyme ADAR1 as a potential regulator for T-cell fate determination during clonal selection, which, in turn, contributes to immunologic homeostasis.