title: Lymphocyte-stromal cell interaction induces IL-7 expression by interferon regulatory factors.
abstract: The interaction between lymphocytes and stromal cells plays important roles in coordinated development of early lymphocytes. IL-7 is an essential cytokine for early lymphocyte development produced by stromal cells in the thymus and bone marrow. Although IL-7 is induced by interaction of early lymphocytes and stromal cells, its molecular basis is still unknown. To address this question, we employed co-culture system with an IL-7-dependent pre-B cell line, DW34, and a thymic stromal cell line, TSt-4. Co-culture with DW34 cells enhanced the levels of IL-7 transcripts in TSt-4 cells. Interestingly, the co-culture also induced transcripts of IFN-α and IFN-β but not of IFN-γ. In addition, exogenous IFN-β stimulation increased the levels of IL-7 transcripts in TSt-4 cells. Next, to elucidate the molecular mechanism of IL-7 induction, we analyzed the IL-7 promoter activity by reporter assay. The IL-7 promoter showed specific transcriptional activity in TSt-4 cells. An interferon-stimulated response element (ISRE) in the IL-7 promoter was essential for the induction of IL-7 transcription by both co-culture and IFN-β stimulation. Finally, overexpression of wild-type and dominant-negative forms of interferon regulatory factors (IRFs) activated and repressed, respectively, the IL-7 promoter in TSt-4 cells. Collectively, these results suggested that IRFs activated by lymphocyte adhesion induce IL-7 transcription through ISRE in stromal cells and that type I IFNs may be involved in the activation of IRFs. Thus, this study implied a physiological function of the IFN/IRF signal during lymphocyte development.
authors: Laboratory of Biological Protection, Department of Biological Responses, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.
authors: Miho
authors: M
authors: Sekai
authors: Shizue
authors: S
authors: Tani-ichi
authors: Mitsutoshi
authors: M
authors: Yoneyama
authors: Takashi
authors: T
authors: Fujita
authors: Tatsuo
authors: T
authors: Kina
authors: Koichi
authors: K
authors: Ikuta
mesh_terms: D000818:Animals; D001483:Base Sequence; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D018920:Coculture Techniques; D050835:Interferon Regulatory Factors / Q000235:genetics* / Q000378:metabolism*; D016899:Interferon-beta / Q000494:pharmacology; D007372:Interferons / Q000235:genetics / Q000378:metabolism; D015851:Interleukin-7 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011401:Promoter Regions, Genetic; D017154:Stromal Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D050835:Interferon Regulatory Factors; D015851:Interleukin-7; D016899:Interferon-beta; D007372:Interferons