| First Author | Sekai M | Year | 2013 |
| Journal | Mol Immunol | Volume | 54 |
| Issue | 3-4 | Pages | 378-85 |
| PubMed ID | 23376291 | Mgi Jnum | J:197097 |
| Mgi Id | MGI:5490829 | Doi | 10.1016/j.molimm.2013.01.002 |
| Citation | Sekai M, et al. (2013) Lymphocyte-stromal cell interaction induces IL-7 expression by interferon regulatory factors. Mol Immunol 54(3-4):378-85 |
| abstractText | 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-alpha and IFN-beta but not of IFN-gamma. In addition, exogenous IFN-beta 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-beta 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. |
