The effect of hoxb4 on self-renewal activity of memory t-cells

hoxb4对记忆T细胞自我更新活性的影响

• 批准号: 342301-2008
• 负责人: Bijl, Janetta
• 金额: $ 2.19万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2008
• 资助国家: 加拿大
• 起止时间: 2008-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=399831
• 关键词: effect; hoxb4; self; renewal; activity

Self-renewal is the division of a cell that results in the generation of a daughter cell with identical properties as the parental cell. This property is characteristic for hematopoietic stem cells (HSCs), enabling them to maintain the stem cell pool for the supply of blood cells throughout the life-time of an organism, and memory T and B cells. Memory T and B cells are responsible for long-term protection of the organism against re-infection. They develop from lymphocytes that are activated for immune response upon contact with viral or bacterial molecules. These lymphocytes undergo a massive expansion and differentiation to eliminate the pathogen. Most of them die after, but a few escapes and become memory lymphocytes that slowly turn over or self-renewal. The molecular mechanism that regulates self-renewal processes in HSCs and memory B and T cells is poorly known. Recent studies suggest that the same genes might control self-renewal in both HSCs and memory T-cells. One gene, Hoxb4, has been found to expand HSC populations, thus determining self-renewal divisions of HSCs. We hypothesize that Hoxb4 also expand the population of memory T cells. We will use a mouse model to analyse the effect of Hoxb4 on self-renewal expansion of memory T cells. If Hoxb4 determines self-renewal of memory T cells, we could not only use Hoxb4 to expand memory T cells for therapeutic use, but the more accessible memory T-cells could serve as a model to elucidate downstream targets of Hoxb4 driven self-renewal of hematopoietic stem cells and provide a source of cells to identify interacting proteins of Hoxb4 in self-renewal function as well.

自我更新是细胞分裂，导致产生具有与亲本细胞相同性质的子细胞。这种性质是造血干细胞（HSC）的特征，使它们能够维持干细胞库，用于在生物体的整个生命周期中供应血细胞以及记忆T和B细胞。记忆T和B细胞负责长期保护机体免受再次感染。它们由淋巴细胞发展而来，淋巴细胞在与病毒或细菌分子接触时被激活以产生免疫反应。这些淋巴细胞进行大规模的扩增和分化，以消除病原体。它们中的大多数在之后死亡，但少数逃脱并成为记忆淋巴细胞，慢慢地翻转或自我更新。调控HSC和记忆B和T细胞自我更新过程的分子机制知之甚少。最近的研究表明，相同的基因可能控制HSC和记忆T细胞的自我更新。已经发现一种基因Hoxb4可以扩增HSC群体，从而决定HSC的自我更新分裂。我们假设Hoxb4也扩大了记忆T细胞的群体。我们将使用小鼠模型来分析Hoxb4对记忆T细胞自我更新扩增的影响。如果Hoxb4决定记忆T细胞的自我更新，我们不仅可以使用Hoxb4扩增记忆T细胞用于治疗用途，而且更易接近的记忆T细胞可以作为阐明Hoxb4驱动的造血干细胞自我更新的下游靶点的模型，并提供细胞来源以鉴定Hoxb4在自我更新功能中的相互作用蛋白。