Autoimmune cardiac-specific T cell responses in dilated cardiomyopathy

Jane‐wit, Dan; Tuohy, Vincent K.

doi:10.1016/j.ijcard.2006.05.007

Cited by 10 publications

(3 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, in contrast to normal cardiac tissues, activated makers were detected in approximately 40% of both CD4 + and CD8 + heart-tissue T cells [ 35 ]. Our study demonstrated an obvious ratio of T cell CD4 memory activated, T cell regulatory Tregs, and neutrophils between DCM and control donors which was consistent with the previous study [ 36 ].…”

Section: Discussionsupporting

confidence: 93%

Construction and evaluation of immune-related diagnostic model in patients with heart failure caused by idiopathic dilated cardiomyopathy

Xu,

Wu,

Chen

2024

BMC Cardiovasc Disord

View full text Add to dashboard Cite

Objective The purpose of the study was to construct the potential diagnostic model of immune-related genes during the development of heart failure caused by idiopathic dilated cardiomyopathy. Method GSE5406 and GSE57338 were downloaded from the GEO website (https://www.ncbi.nlm.nih.gov/geo/). CIBERSORT was used for the evaluation of immune infiltration in idiopathic dilated cardiomyopathy (DCM) of GSE5406. Differently expressed genes were calculated by the limma R package and visualized by the volcano plot. The immune-related genes were downloaded from Immport, TISIDB, and InnateDB. Then the immune-related differential genes (IRDGs) were acquired from the intersection. Protein–protein interaction network (PPI) and Cytoscape were used to visualize the hub genes. Three machine learning methods such as random forest, logical regression, and elastic network regression model were adopted to construct the prediction model. The diagnostic value was also validated in GSE57338. Results Our study demonstrated the obvious different ratio of T cell CD4 memory activated, T cell regulatory Tregs, and neutrophils between DCM and control donors. As many as 2139 differential genes and 274 immune-related different genes were identified. These genes were mainly enriched in lipid and atherosclerosis, human cytomegalovirus infection, and cytokine-cytokine receptor interaction. At the same time, as many as fifteen hub genes were identified as the IRDGs (IFITM3, IFITM2, IFITM1, IFIT3, IFIT1, HLA-A, HLA-B, HLA-C, ADAR, STAT1, SAMHD1, RSAD2, MX1, ISG20, IRF2). Moreover, we also discovered that the elastic network and logistic regression models had a higher diagnostic value than that of random forest models based on these hub genes. Conclusion Our study demonstrated the pivotal role of immune function during the development of heart failure caused by DCM. This study may offer new opportunities for the detection and intervention of immune-related DCM.

show abstract

Section: Discussionsupporting

confidence: 93%

Construction and evaluation of immune-related diagnostic model in patients with heart failure caused by idiopathic dilated cardiomyopathy

Xu,

Wu,

Chen

2024

BMC Cardiovasc Disord

View full text Add to dashboard Cite

show abstract

“…They can regulate germinal center response by controlling the levels of Tfh and B cells and play a critical role in maintaining immune tolerance and regulating immune activation ( 18 , 19 ). In DCM pathogenesis, active inflammation and persistent immune activation may reduce the levels of Tfr; then, Tfh and germinal center B cell proliferation and activation are out of control, as well as the production of related antibodies, which accelerates myocardial injury in patients with DCM ( 20 ). This study aimed to demonstrate the importance of changes in Tfr frequency and Tfr/Tfh ratio in DCM.…”

Section: Discussionmentioning

confidence: 99%

Decreased circulating follicular regulatory T cells in patients with dilated cardiomyopathy

Liu

Zhang

Han

2021

Braz J Med Biol Res

View full text Add to dashboard Cite

Follicular regulatory T cells (Tfr) have critical functions in inflammatory and autoimmune disorders. The main purpose of the current work was to assess Tfr cell frequency in patients with dilated cardiomyopathy (DCM). Flow cytometry showed that, compared with normal controls, DCM cases showed markedly reduced Tfr cell rates and Tfr/Tfh ratios, but significantly increased follicular helper T cell (Tfh) rates. Correlation analysis showed that the Tfr rate in DCM patients was positively correlated with left ventricular ejection fraction (LVEF), and negatively correlated with N-terminal brain natriuretic peptide (NT-proBNP) levels. Lower Foxp3 and higher Bcl-6, ICOS, and PD-1 mRNA expression levels were found in patients with DCM. In addition, plasma interleukin (IL)-6, tumor necrosis factor (TNF)-a, and IL-21 levels were significantly increased in DCM cases. Moreover, IgG and IgG3 levels were also elevated in individuals with DCM. Correlation analysis showed that the Tfr rate in DCM patients was negatively correlated with IgG and IgG3, while the Tfh rate was positively correlated with IgG and IgG3. Changes in circulating Tfr levels may have a critical immunomodulatory function in DCM and may become a new therapeutic target for DCM.

show abstract

“…Thus, it is entirely possible to generate chronic autoimmune T cell responses that persist in heart autoantigens through memory T cell responses following a single event leading to cardiac injuries, such as ischemia or infection. These persistent, chronic cardiac aggressive T-cell responses likely predispose patients to physiological decompensation and DCM over time [ 63 ].…”

Section: Discussionmentioning

confidence: 99%

Immune Mechanism, Gene Module, and Molecular Subtype Identification of Astragalus Membranaceus in the Treatment of Dilated Cardiomyopathy: An Integrated Bioinformatics Study

Chen

Han

et al. 2021

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Astragalus membranaceus has complex components as a natural drug and has multilevel, multitarget, and multichannel effects on dilated cardiomyopathy (DCM). However, the immune mechanism, gene module, and molecular subtype of astragalus membranaceus in the treatment of DCM are still not revealed. Microarray information of GSE84796 was downloaded from the GEO database, including RNA sequencing data of seven normal cardiac tissues and ten DCM cardiac tissues. A total of 4029 DCM differentially expressed genes were obtained, including 1855 upregulated genes and 2174 downregulated genes. GO/KEGG/GSEA analysis suggested that the activation of T cells and B cells was the primary cause of DCM. WGCNA was used to obtain blue module genes. The blue module genes are primarily ADCY7, BANK1, CD1E, CD19, CD38, CD300LF, CLEC4E, FLT3, GPR18, HCAR3, IRF4, LAMP3, MRC1, SYK, and TLR8, which successfully divided DCM into three molecular subtypes. Based on the CIBERSORT algorithm, the immune infiltration profile of DCM was analyzed. Many immune cell subtypes, including the abovementioned immune cells, showed different levels of increased infiltration in the myocardial tissue of DCM. However, this infiltration pattern was not obviously correlated with clinical characteristics, such as age, EF, and sex. Based on network pharmacology and ClueGO, 20 active components of Astragalus membranaceus and 40 components of DMCTGS were obtained from TCMSP. Through analysis of the immune regulatory network, we found that Astragalus membranaceus effectively regulates the activation of immune cells, such as B cells and T cells, cytokine secretion, and other processes and can intervene in DCM at multiple components, targets, and levels. The above mechanisms were verified by molecular docking results, which confirmed that AKT1, VEGFA, MMP9, and RELA are promising potential targets of DCM.

show abstract

Autoimmune cardiac-specific T cell responses in dilated cardiomyopathy

Cited by 10 publications

References 52 publications

Construction and evaluation of immune-related diagnostic model in patients with heart failure caused by idiopathic dilated cardiomyopathy

Construction and evaluation of immune-related diagnostic model in patients with heart failure caused by idiopathic dilated cardiomyopathy

Decreased circulating follicular regulatory T cells in patients with dilated cardiomyopathy

Immune Mechanism, Gene Module, and Molecular Subtype Identification of Astragalus Membranaceus in the Treatment of Dilated Cardiomyopathy: An Integrated Bioinformatics Study

Contact Info

Product

Resources

About