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Interleukin-7—Dependent Interaction of Dendritic Epidermal T Cells with Keratinocytes

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      Dendritic epidermal T cells (DETC), a member of the epithelial tissue-type γδ T-cell family, are characterized by their exclusive residence within mouse epidermis, their dendritic morphology, and their monoclonal nature in the T-cell—receptor configuration. Here we review our recent studies on the interleukin (IL)-7—dependent interaction of DETC with neighboring keratinocytes. Keratinocytes express constitu-tively the mRNAs for IL-7 and secrete biologically relevant amounts of IL-7. This cytokine, in turn, serves as a growth factor for DETC, as evidenced by the proliferative responses to recombinant or kerati-nocyte-derived IL-7 of the 7-17 DETC line and of DETC freshly purified from mouse skin. The 7–17 DETC line undergoes apoptotic cell death in response to external stimuli known to deplete DETC in situ (e.g., ultraviolet ? radiation or corticosteroid treatment), and IL-7 prevents this apoptosis, thereby promoting long-term survival. These results document the crucial role played by IL-7 in maintaining the survival and growth of DETC in epidermis. IL-7 mRNA expression in keratinocytes is abrogated by ultraviolet ? radiation, whereas it is up-regulated by interferon-γ, which is secreted by DETC upon activation. More specifically, interferon-γ induces the preferential expression of truncated forms (2.6 and 1.5 kb) of IL-7 transcripts, in addition to the 2.9- and 1.7-kb transcripts that are expressed constitutively, and this regulation occurs through the usage of alternative transcription initiation sites. These results suggest unique pathways through which IL-7 production is regulated in keratinocytes by external stimuli (e.g., ultraviolet B) as well as T-cell-derived cytokines (e.g., interferon-γ). We propose that kera-tinocyte-derived IL-7 is an essential component of the epidermal cytokine milieu. J Invest Dermatol 105: 50S-53S, 1995