Decreased circulating follicular regulatory T cells in patients with dilated cardiomyopathy

Abstract

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.

Bioinformatics prediction of potential mechanisms and biomarkers underlying dilated cardiomyopathy

“…Additionally, Zhao et al [ 18 ] reported that COL1A2 may participate in DCM pathogenesis by regulating the cardiac remodeling characterized by collagen deposition in the extracellular matrix[ 56 ]. Consistent with our results, Liu et al [ 53 ] identified STAT3 as a hub gene in DCM via bioinformatic analysis. Other studies have also indicated a role of STAT3 in DCM.…”

“…Wang et al [ 52 ] reported that elevated IL-17 levels are significantly associated with DCM incidence and progression. Additionally, the serum levels of other inflammatory factors such as IL-6, tumor necrosis factor-α, and IL-21 are significantly increased in DCM patients[ 53 ]. Thus, the IL-17 signaling pathway may be one of the major signaling pathways involved in the development of DCM.…”

“…Notably, compared with the control group, the DCM group had more infiltrated plasma cells and fewer infiltrated B memory cells, T follicular helper cells, and resting DCs. However, Liu et al [ 53 ] have demonstrated that, compared with healthy controls, DCM patients have more infiltrated T follicular helper cells and fewer T follicular regulatory cells, and infiltration of T follicular regulatory cells is positively correlated with left ventricular ejection fraction.…”

Identification and Verification of Feature Biomarkers Associated With Immune Cells in Dilated Cardiomyopathy by Bioinformatics Analysis

“…For example, it is been reported that polarization of macrophages towards M2 was associated with ventricular remodeling and poor long-term prognosis in DCM ( Nakayama et al, 2017 ). In addition, a significant increase of the number of Th1 and Th17 cells was observed while the number of Treg cells decreased in DCM patients ( Wei et al, 2017 ; Liu et al, 2021 ). Infiltrated immune cells release cytokines and chemokines, such as TGF-β1, IL-1β, and TNF, promoting collagen deposition, fibrosis and cardiac remodeling ( Schultheiss et al, 2019 ).…”

The yin/yang balance of the MHC-self-immunopeptidome

“…Additionally, histone peptides have also been shown to have immunosuppressive activity by activating a subtype of T reg, named follicular regulatory T cells (T frs ) (CXCR5 high PD-1 high and FoxP3 + ), which are located in B cell follicles of secondary lymphoid organs. T frs play pivotal roles in regulating B cell responses and inhibiting the development of auto-Ab ( 88 – 91 ). Histones and nuclear proteins have been shown to induce T frs expansion and up-regulation of immunosuppressive genes ( 92 ).…”