Hedgehog signalling in peripheral T cell differentiation and function

外周 T 细胞分化和功能中的 Hedgehog 信号传导

• 批准号: MR/P000843/1
• 负责人: Tessa Crompton
• 金额: $ 63.51万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 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=MR%2FP000843%2F1
• 关键词: Hedgehog; signalling; peripheral; cell; differentiation

T cells are white blood cells that enable us to fight infectious disease and help us to get rid of cancer. They are important both because they can attack pathogens and cancer cells themselves and also because they control the immune response of other cell types. This project will investigate how three proteins called Hedgehog proteins help to control T cell function. Hedgehog proteins are molecules that are secreted to send signals from one cell to other neighbouring cells. They are essential during development in the foetus as they control the shape of our bodies and the formation of many different types of tissue. After birth Hedgehog proteins are still very important because they regulate many self-renewing tissues in our bodies, such as gut and skin and lung. Hedgehog proteins are also involved in cancer and are secreted by some tumours and inhibiting them is a treatment for some types of cancer. This project will investigate what signals Hedgehog proteins give to T cells and how Hedgehog proteins influence the immune response. We will also test what effect secretion of Hedgehog proteins by tumours has on the way T cells respond to the tumour.

T细胞是白色血细胞，它使我们能够对抗传染病，并帮助我们摆脱癌症。它们很重要，因为它们可以攻击病原体和癌细胞本身，还因为它们控制其他细胞类型的免疫反应。该项目将研究三种称为Hedgehog蛋白的蛋白质如何帮助控制T细胞功能。刺猬蛋白是一种分泌的分子，可以将信号从一个细胞发送到其他相邻细胞。它们在胎儿发育过程中至关重要，因为它们控制着我们身体的形状和许多不同类型组织的形成。出生后，刺猬蛋白仍然非常重要，因为它们调节我们体内许多自我更新的组织，如肠道、皮肤和肺。Hedgehog蛋白也与癌症有关，由一些肿瘤分泌，抑制它们是治疗某些类型癌症的一种方法。该项目将研究Hedgehog蛋白质给T细胞的信号以及Hedgehog蛋白质如何影响免疫反应。我们还将测试肿瘤分泌Hedgehog蛋白对T细胞对肿瘤反应的影响。

项目成果

IFITM proteins drive type 2 T helper cell differentiation and exacerbate allergic airway inflammation.

IFITM蛋白驱动2 T型辅助细胞分化和加剧过敏性气道炎症。

• DOI: 10.1002/eji.201847692
• 发表时间: 2019-01
• 期刊: European journal of immunology
• 影响因子: 5.4
• 作者: Yánez DC;Sahni H;Ross S;Solanki A;Lau CI;Papaioannou E;Barbarulo A;Powell R;Lange UC;Adams DJ;Barenco M;Ono M;D'Acquisto F;Furmanski AL;Crompton T
• 通讯作者: Crompton T

Gli3 in fetal thymic epithelial cells promotes thymocyte positive selection and differentiation by repression of Shh.

• DOI: 10.1242/dev.146910
• 发表时间: 2018-01-31
• 期刊: Development (Cambridge, England)
• 作者: Solanki A;Yanez DC;Ross S;Lau CI;Papaioannou E;Li J;Saldaña JI;Crompton T
• 通讯作者: Crompton T

Foxa1 and Foxa2 in thymic epithelial cells (TEC) regulate medullary TEC and regulatory T-cell maturation.

• DOI: 10.1016/j.jaut.2018.07.009
• 发表时间: 2018-09
• 期刊: Journal of autoimmunity
• 影响因子: 12.8
• 作者: Lau CI;Yánez DC;Solanki A;Papaioannou E;Saldaña JI;Crompton T
• 通讯作者: Crompton T

The kinesin motor protein Kif7 is required for T-cell development and normal MHC expression on thymic epithelial cells (TEC) in the thymus.

• DOI: 10.18632/oncotarget.15241
• 发表时间: 2017-04-11
• 期刊: Oncotarget
• 作者: Lau CI;Barbarulo A;Solanki A;Saldaña JI;Crompton T
• 通讯作者: Crompton T

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