Functional subsets of circulating follicular helper T cells in patients with atherosclerosis

Talepoor, Atefe Ghamar; Khosropanah, Shahdad; Doroudchi, Mehrnoosh

doi:10.14814/phy2.14637

Cited by 9 publications

(7 citation statements)

References 47 publications

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“…The role and significance of cTfh still need to be better defined. 42 , 43 Despite initial reports that cTfh may resemble GC Tfh of secondary lymphoid organs, 3 the vast majority of the current data suggest that cTfh are those that have never entered the GC and, thus, may more closely resemble pre-Tfh. The clinical cardiovascular relevance of Tfh–MZB cell interaction merits further investigation.…”

Section: Discussionmentioning

confidence: 69%

Marginal zone B cells produce ‘natural’ atheroprotective IgM antibodies in a T cell–dependent manner

Harrison,

Newland,

Jiang

et al. 2024

Cardiovascular Research

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Aims The adaptive immune response plays an important role in atherosclerosis. In response to a high-fat/high-cholesterol (HF/HC) diet, marginal zone B (MZB) cells activate an atheroprotective programme by regulating the differentiation and accumulation of ‘poorly differentiated’ T follicular helper (Tfh) cells. On the other hand, Tfh cells activate the germinal centre response, which promotes atherosclerosis through the production of class-switched high-affinity antibodies. We therefore investigated the direct role of Tfh cells and the role of IL18 in Tfh differentiation in atherosclerosis. Methods and results We generated atherosclerotic mouse models with selective genetic deletion of Tfh cells, MZB cells, or IL18 signalling in Tfh cells. Surprisingly, mice lacking Tfh cells had increased atherosclerosis. Lack of Tfh not only reduced class-switched IgG antibodies against oxidation-specific epitopes (OSEs) but also reduced atheroprotective natural IgM-type anti-phosphorylcholine (PC) antibodies, despite no alteration of natural B1 cells. Moreover, the absence of Tfh cells was associated with an accumulation of MZB cells with substantially reduced ability to secrete antibodies. In the same manner, MZB cell deficiency in Ldlr−/− mice was associated with a significant decrease in atheroprotective IgM antibodies, including natural anti-PC IgM antibodies. In humans, we found a positive correlation between circulating MZB-like cells and anti-OSE IgM antibodies. Finally, we identified an important role for IL18 signalling in HF/HC diet–induced Tfh. Conclusion Our findings reveal a previously unsuspected role of MZB cells in regulating atheroprotective ‘natural’ IgM antibody production in a Tfh-dependent manner, which could have important pathophysiological and therapeutic implications.

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Section: Discussionmentioning

confidence: 69%

Marginal zone B cells produce ‘natural’ atheroprotective IgM antibodies in a T cell–dependent manner

Harrison,

Newland,

Jiang

et al. 2024

Cardiovascular Research

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“…The importance of CD4 + T cells in atherogenesis has been highlighted by animal studies showing that transfer of CD4 + T cells aggravates, whilst CD4 + T cell deficiency attenuates atherosclerosis 41 . In the meantime, previous study found that the increased frequencies of T follicular helper cell may suggest the inflammatory response and atherosclerosis progression 42 . CD56dim natural killer cells was a subset of natural killer cells and is best-known by their cytotoxic functions.…”

Section: Discussionmentioning

confidence: 98%

Identification of hub genes and transcription factors in patients with primary gout complicated with atherosclerosis

Xiao,

Lin,

Zhan

2024

Sci Rep

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Evidence shows that primary gout is prone to develop to atherosclerosis, but the mechanism of its occurrence is still not fully clarified. The aim of this study was to explore the molecular mechanism of the occurrence of this complication in gout. The gene expression profiles of primary gout and atherosclerosis were downloaded from the gene expression omnibus database. Overlapping differentially expressed genes (DEGs) between gout and atherosclerosis were identified. The biological roles of common DEGs were explored through enrichment analyses. Hub genes were identified using protein–protein interaction networks. The immune infiltrations of 28 types of immune cells in gout and control samples from GSE160170 were evaluated by the ssGSEA method. Transcription factors (TFs) were predicted using Transcriptional Regulatory Relationships Unraveled by Sentence Based Text Mining (TRRUST) database. A total of 168 overlapping DEGs were identified. Functional enrichment analyses indicated that DEGs were mostly enriched in chemokine signaling pathway, regulation of actin cytoskeleton, and TNF signaling pathway. CytoScape demonstrated 11 hub genes and two gene cluster modules. The immune infiltration analysis showed that the expression of DEGs in gout was significantly upregulated in activated CD4 T cells, gamma delta T cells, T follicular helper cell, CD56dim natural killer cells, and eosinophil. TRRUST predicted one TF, RUNX family transcription factor 1. Our study explored the pathogenesis of gout with atherosclerosis and discovered the immune infiltration of gout. These results may guide future experimental research and clinical transformation.

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“…Tfh are characterized by the expression of transcriptional factor Bcl-6 (B cell lymphoma 6) as well as CXCR5 and PD-1 (programmed death-1) ( 177 , 178 ). A circulating subpopulation is characterized by CXCR3 and CCR6 expression and can be divided on cTfh1 (CXCR3 + CCR6 − ; producing IFNγ), cTfh2 (CXCR3 − CCR6 − ; secreting IL‐4, IL‐5, and IL‐13), and cTfh17 (CXCR3 − CCR6 + ; producing IL‐17A and IL‐22) subsets ( 179 ). Tfh cells have been implicated to the regulation of autoimmune and inflammatory diseases including CVD.…”

Section: Adaptive Immunitymentioning

confidence: 99%

“…Their presence had been detected in the aortic wall ( 180 ) and CXCR3+ Tfh cells were found elevated in atherogenic environment ( 177 , 178 ). Moreover, decreased frequency of cTfh1 and increased frequency of cTfh2 and cTfh17 had been described in patients with atherosclerosis compared to healthy controls ( 179 ). The genetic ablation of Bcl-6 in CD4 + T cells slightly reduce atherosclerotic plaque size in Apoe -/- mice ( 178 ).…”

Section: Adaptive Immunitymentioning

confidence: 99%

Immune and inflammatory mechanisms of abdominal aortic aneurysm

Márquez-Sánchez

Koltsova

2022

Front. Immunol.

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Abdominal aortic aneurysm (AAA) is a life-threatening cardiovascular disease. Immune-mediated infiltration and a destruction of the aortic wall during AAA development plays significant role in the pathogenesis of this disease. While various immune cells had been found in AAA, the mechanisms of their activation and function are still far from being understood. A better understanding of mechanisms regulating the development of aberrant immune cell activation in AAA is essential for the development of novel preventive and therapeutic approaches. In this review we summarize current knowledge about the role of immune cells in AAA and discuss how pathogenic immune cell activation is regulated in this disease.

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Functional subsets of circulating follicular helper T cells in patients with atherosclerosis

Cited by 9 publications

References 47 publications

Marginal zone B cells produce ‘natural’ atheroprotective IgM antibodies in a T cell–dependent manner

Marginal zone B cells produce ‘natural’ atheroprotective IgM antibodies in a T cell–dependent manner

Identification of hub genes and transcription factors in patients with primary gout complicated with atherosclerosis

Immune and inflammatory mechanisms of abdominal aortic aneurysm

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