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-beta 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 alpha E beta 7 integrin CD103, known to affect migration and epithelial retention of DETCs. It also regulates expression of IL-2 receptor (IL-2R beta) that mediates cell proliferation in response to IL-2 or IL-15. In the absence of Runx3, the reduction in CD103 and IL-2R beta 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 CD 103 and IL-2R beta 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. (c) 2006 Elsevier Inc. All rights reserved.