Interleukin-7-dependent interaction of dendritic epidermal t cells with keratinocytes

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 constitutively 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 keratinocyte-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 B 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 B 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 keratinocyte-derived IL-7 is an essential component of the epidermal cytokine milieu.