Runx3 regulates dendritic epidermal T cell development

The Runx3 transcription factor regulates development of T cells during thymopoiesis and TrkC sensory neurons during dorsal root ganglia neurogenesis. It also mediates transforming growth factor-β signaling in dendritic cells and is essential for development of skin Langerhans cells. Here, we report that Runx3 is involved in the development of skin dendritic epidermal T cells (DETCs); an important component of tissue immunoregulation. In developing DETCs, Runx3 regulates expression of the αEβ7 integrin CD103, known to affect migration and epithelial retention of DETCs. It also regulates expression of IL-2 receptor β (IL-2Rβ) that mediates cell proliferation in response to IL-2 or IL-15. In the absence of Runx3, the reduction in CD103 and IL-2Rβ expression on Runx3−/− DETC precursors resulted in impaired cell proliferation and maturation, leading to complete lack of skin DETCs in Runx3−/− mice. The data demonstrate the requirement of Runx3 for DETCs development and underscore the importance of CD103 and IL-2Rβ in this process. Of note, while Runx3−/− mice lack both DETCs and Langerhans cells, the two most important components of skin immune surveillance, the mice did not develop skin lesions under pathogen-free (SPF) conditions.