STAT5 Orchestrates Local Epigenetic Changes for Chromatin Accessibility and Rearrangements by Direct Binding to the TCRγ Locus.

The transcription factor STAT5, which is activated by IL-7R, controls chromatin accessibility and rearrangements of the TCRγ locus. Although STAT-binding motifs are conserved in Jγ promoters and Eγ enhancers, little is known about their precise roles in rearrangements of the TCRγ locus in vivo. To address this question, we established two lines of Jγ1 promoter mutant mice: one harboring a deletion in the Jγ1 promoter, including three STAT motifs (Jγ1P(Δ/Δ)), and the other carrying point mutations in the three STAT motifs in that promoter (Jγ1P(mS/mS)).

IL-7 produced by thymic epithelial cells plays a major role in the development of thymocytes and TCRγδ+ intraepithelial lymphocytes.

IL-7 is a cytokine essential for T cell development and survival. However, the local function of IL-7 produced by thymic epithelial cells (TECs) is poorly understood. To address this question, we generated IL-7-floxed mice and crossed them with FoxN1 promoter-driven Cre (FoxN1-Cre) mice to establish knockout mice conditionally deficient for the expression of IL-7 by TECs.

Role of hepatocyte-derived IL-7 in maintenance of intrahepatic NKT cells and T cells and development of B cells in fetal liver.

The liver contains a variety of resident immune cells, such as NK cells, NKT cells, T cells, macrophages, and dendritic cells. However, little is known about how IL-7, which is produced by hepatocytes, functions locally in development and maintenance of liver immune cells. To address this question, we established IL-7-floxed mice and crossed them with albumin promoter-driven Cre (Alb-Cre) transgenic mice to establish conditional knockout of IL-7 in hepatocytes.