STATs are involved in T-cell development downstream of IL-7 receptorPublic
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Cytokines regulate normal cell development and maintenance in vivo. Interleukin-7 Receptor (IL-7R) signaling is critical for lymphocyte development. It has been shown that IL-7R activates "Signal Transducers and Activators of Transcription" (STATs) to promote T cell differentiation. In mouse models lacking IL-7R, no yo T cells develop. Expression of constitutively active Stat5 can restore yo T cell development from IL-7R knockout precursor cells, thus implying that IL-7R signals through Stat5 during yo T cell development. Surprisingly, published data has shown that yo T cell development is not affected in Stat5 deficient adult mice. Our purpose was to examine T cell development that Stat5 knockouts fetuses, specifically to test the hypothesis that yo T cell development is dependent upon Stat5 during fetal stages only. This hypothesis was tested performing Fetal Thymic Organ Culture (FTOC) of Stat5 knockout E19 thymocytes. In Stat5 knockout mice, there was significantly impaired T cell development compared to wild type controls after in vitro culture, demonstrating the importance of STATs during fetal, but not adult, T cell development. We are currently attempting to define the molecular basis of differences between fetal and adult cytokine receptor signaling using mutants of candidate signaling intermediates.
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