biostudies-literatureXufeng RNIAID NIH HHSNHLBI NIH HHSNCI NIH HHS27-32https://www.ebi.ac.uk/biostudies/studies/S-EPMC8974940biostudies-literatureUnknown2(1)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.Blood science (Baltimore, Md.)RNA editing enzyme ADAR1 is required for early T cell development.PMC8974940R01 HL070561R21 AI078094R21 CA158650Cheng TNie DWang QXufeng RWang WYang QfalseRNA editing enzyme ADAR1 is required for early T cell development.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.2020-01-01T00:00:00Z2020 Jan2025-04-19T12:57:30.315Z2025-04-19T12:57:30.315ZS-EPMC89749403539986710.1097/BS9.0000000000000039