In silico neoantigen screening and HLA multimer-based validation identify immunogenic neopeptide in multifocal lung adenocarcinoma.

Background: Mutations commonly occur in cancer cells, arising neoantigen as potential targets for personalized immunotherapy of lung adenocarcinoma (LUAD). However, the substantial heterogeneity observed among individuals and distinct foci within the same patient presents significant challenges in formulating immunotherapy strategies. The aim of the work is to characterize the mutation pattern and identify neopeptides across different patients and diverse foci within the same patients with LUAD.

Dysregulation of mucosal-associated invariant T cells correlates with altered placental microenvironment in preterm birth.

Preterm birth (PTB) is a major problem affecting perinatal health, directly increasing the mortality risk of mother and infant that often results from the breakdown of the maternal-fetal immune balance. Increasing evidence shows the essential role of mucosal-associated invariant T (MAIT) cells to balance antibacterial function and immune tolerance function during pregnancy. However, the phenotype and function of placental MAIT cells and their specific mechanisms in PTB remain unclear.

Distinctly altered lipid components in hepatocellular carcinoma relate to impaired T cell-dependent antitumor immunity.

Background And Aims: T cells are master effectors of anti-tumor immunity in cancer. Recent studies suggest that altered lipid metabolism imposed by the tumor microenvironment constrains anti-tumor immunity. However, the tumor-associated lipid species changes that dampen T cell ability to control tumor progression are not fully understood.

Long-Chain Acylcarnitines Induce Senescence of Invariant Natural Killer T Cells in Hepatocellular Carcinoma.

Unlabelled: CD1d-restricted invariant natural killer T (iNKT) cells actively patrol the liver and possess valuable antitumor potential. However, clinical trials evaluating administration of iNKT cell-specific agonist α-galactosylceramide (α-GalCer) have failed to achieve obvious tumor regression. Improving the efficacy of iNKT cell-based immunotherapy requires a better understanding of the factors restraining the clinical benefits.

Mucosal-associated invariant T cells reduce and display tissue-resident phenotype with elevated IL-17 producing capacity in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is one of the important causes of cancer-related mortality worldwide. Previous studies have demonstrated the crucial roles of mucosal-associated invariant T (MAIT) cells in regulating tumor immunity, while their roles in NSCLC remain largely unknown. The aim of this study is to evaluate clinical relevance of MAIT cells in blood and tumor tissues of patients with NSCLC.

Activation and Functional Alteration of Mucosal-Associated Invariant T Cells in Adult Patients With Community-Acquired Pneumonia.

Community-acquired pneumonia (CAP) remains the significant infectious cause of morbidity and mortality worldwide. Although mucosal-associated invariant T cells (MAIT) play roles in the pathogenesis of children CAP and ICU-associated pneumonia, their roles in adult CAP are largely unexplored. In this study, we investigated the frequency, phenotype, and function of MAIT cells in peripheral blood and bronchoalveolar lavage fluid (BALF) of adult CAP patients.

The Expansion and Cytotoxicity Detection of Human iNKT Cells.

Invariant natural killer T (iNKT) cell is a type of innate-like T cell subsets with both T and NK cell phenotype and functions. They recognize lipid antigens presented by CD1d molecules and can be specifically activated by alpha-galactosylceramide (α-GalCer) in vitro. After activation, iNKT cells expand efficiently and exert direct killing effects.

Mucosal-Associated Invariant T Cell Dysregulation Correlates With Conjugated Bilirubin Level in Chronic HBV Infection.

Background And Aims: Mucosal-associated invariant T (MAIT) cells are nonconventional T cells restricted to major histocompatibility complex class I-related protein 1 (MR1). They are highly abundant in human liver and activated by T-cell receptor (TCR)-dependent and TCR-independent mechanisms to exhibit rapid, innate-like effector responses. However, the roles of MAIT cells in chronic HBV infection are still open for study.

Mitochondrial-targeted ubiquinone alleviates concanavalin A-induced hepatitis via immune modulation.

Background: Despite knowledge regarding the effects of antioxidants in ameliorating oxidative damage, evidence concerning their effects on activated immune cells is lacking. Here, a concanavalin A (Con A)-induced hepatitis mouse model was used to investigate the protective effects and immune regulatory mechanisms of mitochondrial-targeted ubiquinone (MitoQ).

Methods: Wild-type (WT) and CD1d-knockout (CD1d, NKT cell deficient) mice were pretreated with MitoQ and then intravenously injected with a sublethal dose of Con A.

Detection, Expansion, and Isolation of Human MAIT Cells.

Mucosal-associated invariant T (MAIT) cells are a novel subset of innate-like T cells that recognize vitamin B metabolites from a range of microbes presented by MHC class I-related molecules (MR1). The term mucosal-associated invariant T cells derives from the fact that MAIT cells are abundant in the liver and mucosal tissues, and human MAIT cells use a semi-invariant TCR Vα7.2 Jα33 paired with Vβ2 or Vβ13.

Heterogeneity of antigen specificity between HLA-A*02:01 and other frequent Chinese HLA-A2 subtypes detected by a modified autologous lymphocyte-monocyte coculture.

HLA-A2 is the most common serological HLA type among all ethnic groups. Through advances in DNA typing, more than 800 subtypes of HLA-A2 have been identified, and the existence of heterogeneity of antigen specificity among the HLA-A2 subtypes has been suggested by retrospective analyses of allogeneic transplantation patients and by studies of antigen amino acid structure. However, prior to this study, the antigenicity of a given subtype or the mismatch extent between two given subtypes could not be studied in vitro.

Antigen-specific CD8+ memory stem T cells generated from human peripheral blood effectively eradicate allogeneic targets in mice.

Background: As the implantation and long-term existence of tumor-specific T cells in host are the prerequisite for adoptive immunotherapy, memory stem T cells (T) with self-renewal and differentiation capacity show the greatest potential to implant and long-term exhibit function in vivo, compared with other T cells of differentiation stages. Hence, tumor-specific T have become potential candidate for adoptive T cell therapy of cancer. Here, we reported a protocol to generate allogeneic antigen-specific CD8+ T cells from human PBLs.

PMA treated THP-1-derived-IL-6 promotes EMT of SW48 through STAT3/ERK-dependent activation of Wnt/β-catenin signaling pathway.

Colon cancer is one of the most common digestive malignant tumors that leads to high mortality worldwide, and metastasis is the primary cause of cancer-related death. It is well accepted that the epithelial-mesenchymal transition (EMT) plays a key role in the process of metastasis. As a cytokine that macrophage secretes, IL-6 is involved in the progression of tumors, including the invasion and metastasis via kinds of signaling pathways.

Fas/FasL interaction mediates imbalanced cytokine/cytotoxicity responses of iNKT cells against Jurkat cells.

The rapid antitumor cytokine production and direct cytotoxicity confer invariant NKT (iNKT) cells ideal candidates for cancer therapy. However, the therapeutic potential of iNKT cells in T-cell malignant diseases remains elusive, as antigen presentation by T cells (T-T presentation) has been suggested to induce hyporesponsiveness of iNKT cells. In this study, we found discrepancies in iNKT cell responses against two T cell-origin cell lines (Jurkat and Molt-4).

Elevated Hepatic CD1d Levels Coincide with Invariant NKT Cell Defects in Chronic Hepatitis B Virus Infection.

Activation of invariant NKT (iNKT) cells manifests antiviral immune responses in vivo. However, clinical trials have failed to show consistent hepatitis B virus (HBV) DNA reduction postadministration of iNKT cell-specific agonist α-galactosylceramide (α-GalCer). In this study, we aimed to investigate HBV infection-related iNKT cell defects and explore iNKT cell-based therapeutic potential for chronic hepatitis B (CHB).

Betulin from Hedyotis hedyotidea ameliorates concanavalin A-induced and T cell-mediated autoimmune hepatitis in mice.

Hedyotis hedyotidea has been used in traditional Chinese medicine for the treatment of autoimmune diseases. However, the mechanisms underlying for the effect remain unknown. We previously showed that, among 11 compounds extracted from H hedyotidea, betulin produced the strongest suppressive effect on T cell activation.

Serum DKK-1 level in the development of ankylosing spondylitis and rheumatic arthritis: a meta-analysis.

To explore the association of serum Dickkopf-1 (DKK-1) levels with the development of ankylosing spondylitis (AS) and rheumatic arthritis (RA) in humans, databases including PubMed, EBSCO, Springerlink, Ovid, WANFANG and China National Knowledge Infrastructure (CNKI) were searched to identify relevant studies. On the basis of rigorous inclusion and exclusion criteria, case-control studies of the relationships between serum DKK-1 levels and AS and RA published before December 2014 were enrolled. Statistical analyses were performed using Comprehensive Meta-analysis 2.

The role of HO-1 in protection against lead-induced neurotoxicity.

Lead is a pervasive and persistent environmental pollutant that exerts deleterious effects on all living organisms and continues to threaten public health on a global scale. Heme oxygenase-1 (HO-1) is a stress-inducible enzyme that mediates antioxidative and cytoprotective effects to maintain cellular redox homeostasis and protect cells from oxidative stress. This study was designed to explore the role of HO-1 in protection against lead neurotoxicity and the signaling pathways involved.

Interleukin-33 ameliorates ischemic brain injury in experimental stroke through promoting Th2 response and suppressing Th17 response.

Ischemic stroke causes brain injury with activation of an inflammatory response that can contribute to clinical impairment. As a novel cytokine of the interleukin-1 (IL-1) family, IL-33 has been suggested to be involved in regulating pathophysiology and inflammatory responses in the central nervous system (CNS). However, the role and underlying mechanisms of IL-33 in ischemic stroke remain poorly understood.

Anti-inflammatory effects of triptolide by inhibiting the NF-κB signalling pathway in LPS-induced acute lung injury in a murine model.

Triptolide is one of the main active components in the Chinese herb Tripterygium wilfordii Hook F, which has been demonstrated to possess anti‑inflammatory properties. The aim of this study was to investigate the effects of triptolide on lipopolysaccharide (LPS)‑induced acute lung injury (ALI) in mice and to explore the possible mechanisms. Mice were administered LPS intranasally to induce lung injury, and triptolide was administered intraperitoneally 1 h prior to the LPS challenge.

CD8low T-cell subpopulation is increased in patients with chronic hepatitis B virus infection.

Recent studies suggest that CD8(+) T cells with down-regulated CD8 expression (CD3(+)CD8(low) T cells) represented as a distinct phenotype of CD8(+) T cells are increased and linked to disease severity in some chronically persistent infection, such as chronic HIV and parasite infection. However, the role of CD3(+)CD8(low) T cells in the context of chronic HBV infection is poorly understood. In this study, peripheral blood samples of 47 chronic hepatitis B patients and 19 healthy controls were collected and tested for the frequency and phenotype of CD8(low) T cells.

Demineralized dentin matrix composite collagen material for bone tissue regeneration.

Demineralized dentin matrix (DDM) had been successfully used in clinics as bone repair biomaterial for many years. However, particle morphology of DDM limited it further applications. In this study, DDM and collagen were prepared to DDM composite collagen material.