Interleukin-7-dependent interaction of dendritic epidermal T cells with keratinocytes.
Dendritic epidermal T cells (DETC), a member of the epithelial tissue-type gamma delta 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-gamma, which is secreted by DETC upon activation. More specifically, interferon-gamma 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-gamma). We propose that keratinocyte-derived IL-7 is an essential component of the epidermal cytokine milieu.
Takashima
A
A
Department of Dermatology, University of Texas Southwestern Medical Center, Dallas 75235-9069, USA.
Matsue
H
H
Bergstresser
P R
PR
Ariizumi
K
K
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002450:Cell Communication; D016207:Cytokines / Q000502:physiology; D003713:Dendritic Cells / Q000502:physiology*; D000078404:Epidermal Cells; D005786:Gene Expression Regulation; D006801:Humans; D015851:Interleukin-7 / Q000235:genetics / Q000502:physiology*; D015603:Keratinocytes / Q000502:physiology*; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D012871:Skin Diseases / Q000209:etiology; D013601:T-Lymphocytes / Q000502:physiology*; D014466:Ultraviolet Rays
D016207:Cytokines; D015851:Interleukin-7; D012333:RNA, Messenger