Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
Department of Clinical Sciences, Lund University, Skåne University Hospital, 20502 Malmö, Sweden.
Cardiovasc Res. 2018 Jan 1;114(1):180-187. doi: 10.1093/cvr/cvx196.
The role of CD4+ T cells in atherosclerosis has been shown to be dependent on cytokine cues that regulate lineage commitment into mature T helper sub-sets. In this study, we tested the roles of IL-1R1 and MyD88 signalling in CD4+ T cells in atherosclerosis.
We transferred apoe-/-myd88+/+ or apoe-/-myd88-/- CD4+ T cells to T- and B-cell-deficient rag1-/-apoe-/- mice fed high fat diet. Mice given apoe-/-myd88-/- CD4+ T cells exhibited reduced atherosclerosis compared with mice given apoe-/-myd88+/+ CD4+ T cells. CD4+ T cells from apoe-/-myd88-/- produced less IL-17 but similar levels of IFN-γ. Treatment of human CD4+ T cells with a MyD88 inhibitor inhibited IL-17 secretion in vitro. Transfer of il1r1-/- CD4+ T cells recapitulated the phenotype seen by transfer of myd88-/- CD4+ T cells with reduced lesion development and a reduction in Th17 and IL-17 production compared with wild type CD4+ T cell recipients. Relative collagen content of lesions was reduced in mice receiving il1r1-/- CD4+ T cells.
We demonstrate that both IL1R and MyD88 signalling in CD4+ T cells promote Th17 immunity, plaque growth and may regulate plaque collagen levels.
已经表明，CD4+T 细胞在动脉粥样硬化中的作用取决于细胞因子线索，这些线索调节向成熟 T 辅助亚群的谱系定向。在这项研究中，我们测试了 IL-1R1 和 MyD88 信号在动脉粥样硬化中 CD4+T 细胞中的作用。
我们将 apoe-/-myd88+/+或 apoe-/-myd88-/-CD4+T 细胞转移到 T 和 B 细胞缺陷型 rag1-/-apoe-/-小鼠中，并给予高脂肪饮食。与给予 apoe-/-myd88+/+CD4+T 细胞的小鼠相比，给予 apoe-/-myd88-/-CD4+T 细胞的小鼠动脉粥样硬化程度降低。apoe-/-myd88-/-CD4+T 细胞产生的 IL-17 较少，但 IFN-γ 水平相似。用 MyD88 抑制剂处理人 CD4+T 细胞可抑制体外 IL-17 的分泌。与野生型 CD4+T 细胞受者相比，il1r1-/-CD4+T 细胞的转移再现了 myd88-/-CD4+T 细胞的表型，其病变发展减少，Th17 和 IL-17 产生减少。接受 il1r1-/-CD4+T 细胞的小鼠的病变中相对胶原含量减少。
我们证明，CD4+T 细胞中的 IL1R 和 MyD88 信号均促进 Th17 免疫、斑块生长，并可能调节斑块胶原水平。
