Impact of Hedgehog signalling on the T cell receptor (TCR) repertoire

Hedgehog 信号传导对 T 细胞受体 (TCR) 库的影响

• 批准号: 1903458
• 金额: --
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1903458
• 关键词: Impact; Hedgehog; signalling; cell; receptor

We have shown that the Hedgehog signalling pathway regulates T-cell development in the thymus1,2. Sonic hedgehog (Shh) from thymic epithelial cells (TEC) signals to developing thymocytes to regulate their differentiation at key pre-T-cell receptor (pre-TCR) and TCR-dependent check-points1,2. Analysis of TCR-transgenic mice showed that Hh signalling reduced TCR signal strength during pre-TCR and TCR-induced differentiation2,3. We now plan to test the impact of these changes in TCR-signal strength induced by Hedgehog signalling on TCR repertoire selection, by next generation sequencing the TCR and TCR-chain repertoires from facs-sorted thymocyte populations at different stages of their development.

我们已经表明，刺猬信号通路调节T细胞的胸腺发育1，2。来自胸腺上皮细胞（TEC）的Sonic hedgehog（Shh）向发育中的胸腺细胞发出信号，以在关键的前T细胞受体（pre-TCR）和TCR依赖性检查点调节其分化1，2。TCR转基因小鼠的分析显示，在前TCR和TCR诱导的分化期间，Hh信号传导降低TCR信号强度2，3。我们现在计划通过下一代测序来自不同发育阶段的facs分选的胸腺细胞群的TCR和TCR链库，来测试由Hedgehog信号传导诱导的TCR信号强度的这些变化对TCR库选择的影响。

项目成果

The pioneer transcription factors Foxa1 and Foxa2 regulate alternative RNA splicing during thymocyte positive selection.

先驱转录因子 Foxa1 和 Foxa2 在胸腺细胞正选择过程中调节选择性 RNA 剪接。

• DOI: 10.1242/dev.199754
• 发表时间: 2021-08-01
• 期刊: Development (Cambridge, England)
• 作者: Lau CI;Rowell J;Yanez DC;Solanki A;Ross S;Ono M;Crompton T
• 通讯作者: Crompton T

Systemic Pharmacological Smoothened Inhibition Reduces Lung T-Cell Infiltration and Ameliorates Th2 Inflammation in a Mouse Model of Allergic Airway Disease.

• DOI: 10.3389/fimmu.2021.737245
• 发表时间: 2021
• 期刊: Frontiers in immunology
• 影响因子: 7.3
• 作者: Yánez DC;Papaioannou E;Chawda MM;Rowell J;Ross S;Lau CI;Crompton T
• 通讯作者: Crompton T