Th17/Treg Cells Imbalance and GITRL Profile in Patients with Hashimoto’s Thyroiditis

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Increased Frequency of Circulating Follicular Helper T Cells in Patients with Rheumatoid Arthritis

Follicular helper T (Tfh) cells are recognized as a distinct CD4+ helper T-cell subset, which provides for B-cell activation and production of specific antibody responses, and play a critical role in the development of autoimmune disease. So far, only one study investigated the circulating Tfh cells increased in a subset of SLE patients. Since relatively little is known about the Tfh cells in rheumatoid arthritis (RA) patients, in this study, Tfh-cell frequency, related cytokine IL-21, and transcription factor Bcl-6 were investigated in 53 patients with RA and 31 health controls. Firstly, we found that the frequency of CD4+CXCR5+ICOShigh Tfh cells was increased significantly in the peripheral blood of RA patients, compared with that in healthy controls. It is known that Tfh cells are critical for directing the development of an antibody response by germinal centers B cells; secondly, we observed that the Tfh-cell frequency is accompanied by the level of anti-CCP antibody in RA patients. Furthermore, expression of Bcl-6 mRNA and plasma IL-21 concentrations in RA patients was increased. Taken together, these findings have shown that the increased frequency of circulating Tfh cells is correlated with elevated levels of anti-CCP antibody, indicating the possible involvement of Tfh cells in the disease progression of RA

Effect and Mechanism of Polyethylene Glycol (PEG) Used as a Phase Change Composite on Cement Paste

The use of phase change materials (PCMs) in the construction industry is one of the primary strategies for addressing the building industry’s present excessive energy usage. However, since PCMs must be enclosed before being used in construction, their efficiency is limited and their compatibility with concrete is poor. Thus, polyethylene glycol (PEG), a sequence of PCMs that may be put directly into concrete, is the target of this research. The fluidity, mechanical properties, thermal properties, hydration process, and hydration products of PEG-600 cement slurry were examined by TAM, XRD, FTIR, DSC, MALDI, etc., methods in this study. Furthermore, we tested the thermal properties of PEG-800 to confirm that the same depolymerization of PEG occurred in an alkaline environment. When PEG, with a molecular weight of 600 (PEG-600), dose was increased to 10%, both compressive and flexural strength fell by 19% and 18%, respectively. The phase change points of both PEG-600 cement paste and PEG-800 cement paste decreased to 10~15 °C, and the enthalpy of the phase change was about 6 J/g. Additionally, it was discovered that PEG entered the reaction during the hydration step. PEG underwent depolymerization and subsequently formed a complex with Ca2+. However, due to the large dose of PEG used in this investigation, a self-curing effect of PEG in concrete was not seen. The findings of this research suggest a novel use for PCMs: PEG may be directly applied to concrete to fulfill both mechanical and thermal requirements. Additionally, the number of hydration products and phase compositions remained almost constant

Increased Interleukin-23 in Hashimoto’s Thyroiditis Disease Induces Autophagy Suppression and Reactive Oxygen Species Accumulation

Hashimoto’s thyroiditis (HT) represents the most common organ-specific autoimmune disease. Inflammatory factors and reactive oxygen species (ROS) play detrimental roles during the pathogenesis of HT. In this study, we found that thyroid follicular cells (TFCs) from HT patients expressed an elevated level of interleukin-23 (IL-23), which contributed to autophagy suppression and ROS accumulation. Additionally, IL-23-induced autophagy suppression and ROS accumulation in human TFCs was attributed to AKT/mTOR/NF-κB signaling pathway activation. Inhibition of either IL-23 by a specific neutralization antibody, or mTOR by rapamycin, or NF-κB by IKK-16, significantly reversed the autophagy suppression and ROS accumulation. These results demonstrate a key role for IL-23 in HT pathogenesis and provide a potential therapeutic strategy against IL-23 or its signaling pathway in HT

Tumor-Activated TCRγδ+ T Cells from Gastric Cancer Patients Induce the Antitumor Immune Response of TCRαβ+ T Cells via Their Antigen-Presenting Cell-Like Effects

Human γδ T cells display the principal characteristics of professional antigen-presenting cells (APCs), in addition to playing a vital role in immunity through cytokine secretion and their cytotoxic activity. However, it is not clear whether γδ T cells perform APC-like functions under pathological conditions. In this study, we showed that, in contrast to peripheral-derived γδ T cells directly isolated from PBMCs of gastric cancer patients, tumor-activated γδ T cells not only killed tumor cells efficiently but also strongly induced primary CD4+ and CD8+  αβ T cells proliferation and differentiation. More importantly, they abrogated the immunosuppression induced by CD4+CD25+ Treg cells and induced the cytotoxic function of CD8+  αβ T cells from patients with gastric cancer. In conclusion, tumor-activated γδ T cells can induce adaptive immune responses through their APC-like functions, and these cells may be a potentially useful tool in the development of tumor vaccines and immunotherapy

Peli1 impairs microglial Aβ phagocytosis through promoting C/EBPβ degradation.

Amyloid-β (Aβ) accumulation in the brain is a hallmark of Alzheimer's disease (AD) pathology. However, the molecular mechanism controlling microglial Aβ phagocytosis is poorly understood. Here we found that the E3 ubiquitin ligase Pellino 1 (Peli1) is induced in the microglia of AD-like five familial AD (5×FAD) mice, whose phagocytic efficiency for Aβ was then impaired, and therefore Peli1 depletion suppressed the Aβ deposition in the brains of 5×FAD mice. Mechanistic characterizations indicated that Peli1 directly targeted CCAAT/enhancer-binding protein (C/EBP)β, a major transcription factor responsible for the transcription of scavenger receptor CD36. Peli1 functioned as a direct E3 ubiquitin ligase of C/EBPβ and mediated its ubiquitination-induced degradation. Consequently, loss of Peli1 increased the protein levels of C/EBPβ and the expression of CD36 and thus, promoted the phagocytic ability in microglial cells. Together, our findings established Peli1 as a critical regulator of microglial phagocytosis and highlighted the therapeutic potential by targeting Peli1 for the treatment of microglia-mediated neurological diseases