Foxa1/A2, Shh and Gli3 in T lymphocyte development

Foxa1/A2、Shh 和 Gli3 在 T 淋巴细胞发育中的作用

• 批准号: MR/S037764/1
• 负责人: Tessa Crompton
• 金额: $ 69.69万
• 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: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FS037764%2F1
• 关键词: Foxa1; A2; Shh; Gli3; lymphocyte

T-cells are white blood cells that enable us to fight infectious disease by attacking infections and also by coordinating the immune response. T-cells are produced in an organ called the thymus. The thymus is essential, as people born without a thymus have no T-cells and cannot fight infectious disease. The thymus is also important because it ensures that the T-cells that are produced do not not attack our own bodies (they are tolerant to self), and it produces a type of T-cells that are required to dampen down the immune response, called regulatory T-cells. When the thymus does not not work properly, several different kinds of diseases arise: we could become immunodeficient because we do not have enough T-cells; we could develop autoimmune disease such as rheumatoid arthritis or type I diabetes, because our T-cells attack our own bodies and organs; finally, if T-cell expansion and development is not properly controlled we may develop leukaemia (blood cancer). It is very important to understand how the thymus controls the development of T-cells and how it makes T-cells tolerant to self, and produces regulatory T-cells to control the immune response. In this project we will investigate how four proteins, called Foxa1, Foxa2, Shh and Gli3 contribute to controlling how the thymus produces T-cells, how it makes the T-cells self tolerant, and how the thymus controls the production of regulatory T-cells.

T细胞是白细胞，使我们能够通过攻击感染和协调免疫反应来抵抗传染病。 T细胞在一个称为胸腺的器官中产生。胸腺是必不可少的，因为没有胸腺的人出生的人没有T细胞，无法抵抗传染病。胸腺也很重要，因为它可以确保产生的T细胞不会不会攻击我们自己的身体（它们宽容自我），并且会产生一种抑制免疫反应所需的T细胞，称为调节性T细胞。当胸腺无法正常工作时，会出现几种不同类型的疾病：我们可能会变得免疫缺陷，因为我们没有足够的T细胞；我们可以发展自身免疫性疾病，例如类风湿关节炎或I型糖尿病，因为我们的T细胞会攻击我们自己的身体和器官；最后，如果无法正确控制T细胞的扩张和发育，我们可能会发展为白血病（血液癌）。了解胸腺如何控制T细胞的发展以及它如何使T细胞耐受自我，并产生调节性T细胞来控制免疫反应，这一点非常重要。在这个项目中，我们将研究四种称为FOXA1，FOXA2，SHH和GLI3的蛋白如何有助于控制胸腺如何产生T细胞，如何使T细胞自耐受性以及胸腺如何控制调节性T细胞的产生。

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

The Pioneer Transcription Factor Foxa2 Modulates T Helper Differentiation to Reduce Mouse Allergic Airway Disease.

• DOI: 10.3389/fimmu.2022.890781
• 发表时间: 2022
• 期刊: Frontiers in immunology
• 影响因子: 7.3

Distinct T Cell Receptor (TCR) gene segment usage and MHC-restriction between foetal and adult thymus

胎儿和成人胸腺之间不同的 T 细胞受体 (TCR) 基因片段使用和 MHC 限制

• DOI: 10.1101/2023.09.20.558574
• 发表时间: 2023
• 作者: Rowell J

Cryopreservation of mouse thymus depletes thymocytes but supports immune reconstitution on transplantation.

小鼠胸腺的冷冻保存会消耗胸腺细胞，但支持移植时的免疫重建。

• DOI: 10.1002/eji.202350546
• 发表时间: 2023
• 期刊: European journal of immunology
• 影响因子: 5.4
• 作者: Chawda MM

Author Correction: Metabolite and thymocyte development defects in ADA-SCID mice receiving enzyme replacement therapy.

• DOI: 10.1038/s41598-021-03903-7
• 发表时间: 2021-12-15
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Moretti FA;Giardino G;Attenborough TCH;Gkazi AS;Margetts BK;la Marca G;Fairbanks L;Crompton T;Gaspar HB
• 通讯作者: Gaspar HB