Development and function of inflammatory dendritic cells

炎症树突状细胞的发育和功能

• 批准号: BB/M029735/1
• 负责人: Pierre Guermonprez
• 金额: $ 57.85万
• 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: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FM029735%2F1
• 关键词: Development; function; inflammatory; dendritic; cells

The vaccination method relies on the activation and expansion of cells called T lymphocytes that can recognise the antigens of pathogens. After vaccination, these T cells react quicker and better to pathogen encounter and can mediate immune protection. The activation of T lymphocytes is controlled by a family of cells called dendritic cells that capture pathogens and present pathogen derived antigens to T cells on presenter molecules called MHC (major histocompatibility complex). Several populations of dendritic cells have been described. They harbour distinct immune function important for the establishment of protective immunity. However, some members of the dendritic cell family are ill described and their specific contribution to the protective T cell responses not yet defined. In particular, during the small inflammation caused by vaccination (or infection), a new type of cells is produced in large quantities by the immune system called inflammatory DCs (iDCs). How iDCs are produced and to what extent they contribute to the development of protective immune responses has still to be understood. This proposal intends to :- better characterise these cells, - understand how the immune system produces them and - determine how they impact the development of adaptive immunity induced by vaccinationThis research is important for human and animal health because it will enable to produce better vaccines. Indeed understanding iDCs biology is key to tailor vaccine adjuvants that will maximise the induction of protective immune responses required for the success of vaccination.

疫苗接种方法依赖于 T 淋巴细胞的激活和扩增，这种细胞可以识别病原体的抗原。接种疫苗后，这些 T 细胞对病原体的反应更快更好，可以介导免疫保护。 T 淋巴细胞的激活由称为树突状细胞的细胞家族控制，树突状细胞捕获病原体并将病原体衍生的抗原呈递给称为 MHC（主要组织相容性复合体）的呈递分子上的 T 细胞。已经描述了几种树突状细胞群。它们具有独特的免疫功能，对于建立保护性免疫力很重要。然而，对树突细胞家族的一些成员的描述不充分，并且它们对保护性 T 细胞反应的具体贡献尚未确定。特别是，在疫苗接种（或感染）引起的小炎症期间，免疫系统会大量产生一种新型细胞，称为炎性树突状细胞（iDC）。 iDC 是如何产生的以及它们对保护性免疫反应的发展有何贡献仍有待了解。该提案旨在：-更好地表征这些细胞，-了解免疫系统如何产生它们，以及-确定它们如何影响疫苗接种诱导的适应性免疫的发展这项研究对人类和动物健康很重要，因为它将能够生产更好的疫苗。事实上，了解 iDC 的生物学特性是定制疫苗佐剂的关键，从而最大限度地诱导疫苗接种成功所需的保护性免疫反应。

项目成果

Protein tyrosine phosphatase PTPN22 is dispensable for dendritic cell antigen processing and promotion of T-cell activation by dendritic cells.

• DOI: 10.1371/journal.pone.0186625
• 发表时间: 2017
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Clarke F;Jordan CK;Gutiérrez-Martinez E;Bibby JA;Sanchez-Blanco C;Cornish GH;Dai X;Rawlings DJ;Zamoyska R;Guermonprez P;Cope AP;Purvis HA
• 通讯作者: Purvis HA

The protein tyrosine phosphatase PTPN22 negatively regulates presentation of immune complex derived antigens.

• DOI: 10.1038/s41598-018-31179-x
• 发表时间: 2018-08-23
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Clarke F;Purvis HA;Sanchez-Blanco C;Gutiérrez-Martinez E;Cornish GH;Zamoyska R;Guermonprez P;Cope AP
• 通讯作者: Cope AP

Transcriptional and Functional Analysis of CD1c+ Human Dendritic Cells Identifies a CD163+ Subset Priming CD8+CD103+ T Cells

• DOI: 10.1016/j.immuni.2020.06.002
• 发表时间: 2020-08-18
• 期刊: IMMUNITY
• 影响因子: 32.4
• 作者: Bourdely, Pierre;Anselmi, Giorgio;Guermonprez, Pierre
• 通讯作者: Guermonprez, Pierre