CD1d AS A NOVEL REGULATOR OF INNATE IMMUNITY

CD1d 作为先天免疫的新型调节剂

• 批准号: BB/T013710/1
• 负责人: Patricia Barral
• 金额: $ 59.57万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FT013710%2F1
• 关键词: CD1d; NOVEL; REGULATOR; INNATE; IMMUNITY

Toll-like receptors (TLR) are a group of proteins that play a key role in the immune system by functioning as a first barrier for the recognition of pathogens such as virus or bacteria. The recognition of such pathogens by TLRs initiates a cascade of activation of immune cells that ultimately leads to pathogen elimination. However, the inappropriate activation of TLRs can be detrimental for health as in the case of autoimmune diseases or sepsis. Thus, understanding the processes that control the activation of TLRs is critical to modulate the balance between protective and pathogenic immune responses. Recent studies have proposed a role for the lipid cholesterol as a key regulator of TLR signalling. This suggests that controlling the cholesterol synthesis pathways (for instance by using statins) could be a tool to potentiate or dampen immune responses. However, the detailed processes regulating the crosstalk between immune cell activation and cholesterol metabolism remain unclear. The main aim of this proposal is to understand the pathways that link cholesterol metabolism and TLR responses. We will study in-depth the pathways that control TLR activation, investigate how they relate to cholesterol metabolism and evaluate their function during bacterial infection. Understanding the mechanisms regulating TLR activation will help design better strategies for prevention and treatment of infectious and inflammatory diseases.

Toll样受体（TLR）是一组在免疫系统中发挥关键作用的蛋白质，作为识别病原体（如病毒或细菌）的第一道屏障。TLR对这些病原体的识别启动了免疫细胞的级联激活，最终导致病原体消除。然而，TLR的不适当激活可能对健康有害，如在自身免疫性疾病或败血症的情况下。因此，了解控制TLR激活的过程对于调节保护性和致病性免疫应答之间的平衡至关重要。最近的研究提出了一个作用的脂质胆固醇作为一个关键的调节TLR信号。这表明控制胆固醇合成途径（例如通过使用他汀类药物）可能是增强或抑制免疫反应的工具。然而，调节免疫细胞活化和胆固醇代谢之间串扰的详细过程仍不清楚。该提案的主要目的是了解胆固醇代谢和TLR反应之间的联系途径。我们将深入研究控制TLR激活的途径，研究它们如何与胆固醇代谢相关，并评估它们在细菌感染期间的功能。了解调节TLR激活的机制将有助于设计更好的预防和治疗感染性和炎症性疾病的策略。

项目成果

CD1d-dependent rewiring of lipid metabolism in macrophages regulates innate immune responses.

• DOI: 10.1038/s41467-022-34532-x
• 发表时间: 2022-11-07
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Brailey, Phillip M.;Evans, Lauren;Lopez-Rodriguez, Juan Carlos;Sinadinos, Anthony;Tyrrel, Victoria;Kelly, Gavin;O'Donnell, Valerie;Ghazal, Peter;John, Susan;Barral, Patricia
• 通讯作者: Barral, Patricia