Oxidized low-density lipoproteins impair the pro-atherosclerotic effect of granulocyte-macrophage-colony-stimulating factor-producing T helper cells on macrophages
T cells contribute to the pathogenesis of atherosclerosis. However, the presence and function of granulocyte-macrophage-colony-stimulating factor (GM-CSF)-producing T helper (ThGM) cells in atherosclerosis development is unknown. This study aims to characterize the phenotype and function of ThGM cells in experimental atherosclerosis. Atherosclerosis was induced by feeding apolipoprotein E knockout (ApoE-/-) mice with a high-fat diet. Aortic ThGM cells were detected and sorted by flow cytometry. The effect of oxidized low-density lipoprotein (oxLDL) on ThGM cells and the impact of ThGM cells on macrophages were evaluated by flow cytometry, quantitative RT-PCR, oxLDL binding/uptake assay, immunoblotting and foam cell formation assay. We found that GM-CSF+IFN-gamma- ThGM cells existed in atherosclerotic aortas. Live ThGM cells were enriched in aortic CD4+CCR6-CCR8-CXCR3-CCR10+ T cells. Aortic ThGM cells triggered the expression of interleukin-1 beta (IL-1 beta), tumour necrosis factor (TNF), interleukin-6 (IL-6) and C-C motif chemokine ligand 2 (CCL2) in macrophages. Besides, aortic ThGM cells expressed higher CD69 than other T cells and bound to oxLDL. oxLDL suppressed the cytokine expression in ThGM cells probably via inhibiting the signal transducer and activator of transcription 5 (STAT5) signalling. Furthermore, oxLDL alleviated the effect of ThGM cells on inducing macrophages to produce pro-inflammatory cytokines and generate foam cells. The nuclear receptor subfamily 4 group A (NR4A) members NR4A1 and NR4A2 were involved in the suppressive effect of oxLDL on ThGM cells. Collectively, oxLDL suppressed the supportive effect of ThGM cells on pro-atherosclerotic macrophages. ThGM cells express IL-2, TNF, CCL20, IFN-gamma and GM-CSF to induce macrophages to produce pro-inflammatory mediators and form foam cells. However, oxidized low-density lipoprotein binds to CD69 and induces the expression of NR4A1 and NR4A2 in ThGM cells, subsequently down-regulating ThGM-associated cytokines and inhibiting the supportive effect on macrophages.image
基金：
Wuhan Municipal Health and Family Planning Commission Foundation
第一作者机构：[1]Wuhan Univ, Dept Cardiol, Wuhan Hosp 3, Tongren Hosp, 241 Pengliuyang Rd, Wuchang 430060, Hubei, Peoples R China
通讯作者：
通讯机构：[1]Wuhan Univ, Dept Cardiol, Wuhan Hosp 3, Tongren Hosp, 241 Pengliuyang Rd, Wuchang 430060, Hubei, Peoples R China[*1]The Department of Cardiology at Wuhan Third Hospital (Tongren Hospital of Wuhan University), 241 Pengliuyang Road, Wuchang District, Hubei Province, 430060, China.
推荐引用方式(GB/T 7714)：
Xiong Xiaofang,Yan Zheng,Yan Long,et al.Oxidized low-density lipoproteins impair the pro-atherosclerotic effect of granulocyte-macrophage-colony-stimulating factor-producing T helper cells on macrophages[J].SCANDINAVIAN JOURNAL OF IMMUNOLOGY.2024,99(5):doi:10.1111/sji.13362.
APA：
Xiong, Xiaofang,Yan, Zheng,Yan, Long,Yang, Xuexue,Li, Dongsheng&Lin, Guizhen.(2024).Oxidized low-density lipoproteins impair the pro-atherosclerotic effect of granulocyte-macrophage-colony-stimulating factor-producing T helper cells on macrophages.SCANDINAVIAN JOURNAL OF IMMUNOLOGY,99,(5)
MLA：
Xiong, Xiaofang,et al."Oxidized low-density lipoproteins impair the pro-atherosclerotic effect of granulocyte-macrophage-colony-stimulating factor-producing T helper cells on macrophages".SCANDINAVIAN JOURNAL OF IMMUNOLOGY 99..5(2024)
