The mechanisms by which circulating macrophages and their liver counterparts (Kupffer and hepatic stellate cells) alter CD8+ T-cell activity

循环巨噬细胞及其肝脏对应物（枯否细胞和肝星状细胞）改变 CD8 T 细胞活性的机制

• 批准号: RGPIN-2015-05674
• 负责人: Crawley, Angela
• 金额: $ 2.55万
• 依托单位: University of Ottawa
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=590572
• 关键词: mechanisms; circulating; macrophages; their; liver

The orchestration of T-cell responses by innate immune cells such as macrophages is a hallmark of adaptive immunity. The effect of cytokine production and cell-cell contact of macrophage subsets has been well described for CD4+ T-cell subset differentiation, while their control of CD8+ T-cell activity and cytolytic (CTL) function remains unclear. Blood-derived macrophages have been recently described to polarize into M1, M2a, 2b and 2c subsets, establishing inflammatory, immunoregulatory or tissue-repairing cytokine milieus. In addition, the role of tissue-specific macrophages in maintaining immune tolerance and balancing the immune response and tissue destructive effects of infiltrating CD8+ T-cells remains to be fully described. For example, liver resident macrophages (Kupffer cells, KC, and hepatic stellate cells, HSC) have recently been described to polarize to M1- and M2-like phenotypes in non-alcoholic fatty liver disease, yet their potential for M2a, 2b or 2c subset differentiation has not been investigated. The inherent pro- and anti-inflammatory attributes of M1 and M2 subsets may enhance or inhibit CD8+ T-cell activity and CTL function.

先天免疫细胞如巨噬细胞协调t细胞反应是适应性免疫的标志。细胞因子产生和巨噬细胞亚群的细胞-细胞接触对CD4+ t细胞亚群分化的影响已经被很好地描述，而它们对CD8+ t细胞活性和细胞溶解（CTL）功能的控制尚不清楚。血液来源的巨噬细胞最近被描述为M1， M2a， 2b和2c亚群，建立炎症，免疫调节或组织修复细胞因子环境。此外，组织特异性巨噬细胞在维持免疫耐受、平衡浸润性CD8+ t细胞的免疫反应和组织破坏性作用中的作用仍有待充分描述。例如，肝脏巨噬细胞（Kupffer细胞，KC和肝星状细胞，HSC）最近被描述为在非酒精性脂肪肝疾病中极化为M1-和m2样表型，但尚未研究它们向M2a， 2b或2c亚群分化的潜力。M1和M2亚群固有的促炎和抗炎特性可能增强或抑制CD8+ t细胞活性和CTL功能。