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题目:: Transcription profiling of mouse with T cell-specific targeting of TGFI? receptor to investigate cellular mechanisms of fatal early-onset autoimmunity
ID:
状态:: 发布时间June 12, 2008 , 更新时间 March 27, 2012 , 提交时间 Feb. 3, 2006,
物种:: Mus musculus
摘要:: Transforming growth factor-β (TGF-β) has been implicated in the control of differentiation and proliferation of multiple cell types. However, a role for TGF-β in the control of immune homeostasis is not fully understood because of its pleiotropic action. Here we report that complete ablation of the TGF-β signaling in T cells engendered aggressive early-onset, multiorgan, autoimmune-associated lesions with 100% mortality. Peripheral CD4+ and CD8+ T cells with TGF-β-receptor II (TGF-βRII) deficiency activated cytolytic and T helper 1 (Th1) differentiation program in a cell-intrinsic T cell receptor (TCR)-specific fashion. Furthermore, TGF-βRII deficiency blocked the development of canonical CD1d-restricted NKT cells. Instead, it facilitated generation of a highly pathogenic T cell subset exhibiting multiple hallmarks of NK cells and sharply elevated amounts of FasL, perforin, granzymes, and interferon-γ. Thus, TGF-β signaling in peripheral T cells is crucial in restraining TCR activation-dependent Th1, cytotoxic, and NK cell-like differentiation program which, when left unchecked, leads to rapidly progressing fatal autoimmunity. Experiment Overall Design: To better understand the basis for pathogenicity of TGF-βRII-deficient NK1.1+ T cells, we performed gene expression profiling of NK1.1+ and NK1.1− T cell subsets from Tgfbr2fl/fl x CD4-Cre mice. We limited our analysis to CD8+ T cell subsets because NK1.1+ CD8 T cells made up 70% of total NK1.1+ T cells in Tgfbr2fl/fl x CD4-Cre mice, and this T cell subset showed the greatest numerical increase compared to littermate control mice. Thus, in these experiments we used FACS-sorted NK1.1+ and NK1.1− CD8+ T cells from 15- to 17-day-old mutant mice and total CD8+ T cells from Tgfbr2fl/wt x CD4-Cre littermate controls. Experiment Overall Design: mRNA expression profiles of NK1.1+ and NK1.1− CD8+ T cells from Tgfbr2fl/fl x CD4-Cre (KO) mice were compared to NK1.1− T cells from littermate control Tgfbr2fl/WT x CD4-Cre (Control) mice.
实验种类:: transcription profiling by array
样本量:: 3
实验设计:
: 无设计数据
数据号:: E-GEOD-4178, GSE4178
数据状态:: 无法自动分析，您可以尝试手动分析数据。

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