Transcription factor Ets1 regulates the expression of CD122 (IL-2/15Rβ subunit) in developing thymic Vγ5+ dendritic epidermal T cell (DETC) progenitors 2999

Abstract Description Dendritic epidermal T cells (DETC) are a subset of γδ T cells found in the epidermis of mouse skin where they are thought to contribute to epidermal homeostasis and wound healing. DETC progenitors are the first lymphocytes to develop in the fetal thymus at E14 during mouse gestation. They mature in the thymus and then migrate to the epidermis where they are maintained by self-renewal. Recently, we showed that the loss of transcription factor Ets1 leads to absence of DETC in skin. In this study, we examine fetal thymic development of DETC progenitors in Ets1-/- mice. While embryos lacking Ets1 have DETC progenitors in the fetal thymus at embryonic day 16.5, these cells are characterized by significant changes in the expression of multiple maturation markers. Expression of CD122 (IL-2/IL-15 receptor β chain) is decreased in DETC progenitors in Ets1-/- mice. CD122 is required to maintain DETC in skin and indeed no DETC are found in the skin of Ets1-/- mice at postnatal P5 despite progenitors being present in fetal thymus. DETC progenitors from Ets1-deficient fetal thymus show impaired survival when cultured in media containing IL-2 and IL-15. Assessment of Ets1 CUT&RUN indicate potential Ets1 binding sites located within open chromatin of the CD122 gene locus. These data indicate that the main role of Ets1 in regulating DETC numbers may be in its ability to directly bind to/upregulate the expression of the CD122 gene, which is required for the maintenance of DETC in the skin. Funding Sources Supported by R01 AI122720; AAI Careers in Immunology Fellowship to Michael Battaglia Topic Categories Immune Response Regulation: Molecular Mechanisms (IRM)