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 and impaired anti-bacterial potential of mucosal-associated invariant T cells in autoimmune liver diseases.

Autoimmune liver diseases (AILD) encompass a group of conditions in which the immune system mistakenly attacks the liver tissue. Mucosal-associated invariant T (MAIT) cells are enriched in the liver, where they play crucial roles in antibacterial defense and inflammation regulation. Compared to other autoimmune conditions affecting the synovium of the joints, MAIT cells from AILD exhibited a greater deficiency in ratio, elevated activation markers, increased apoptosis, and higher pro-inflammatory cytokines production.

Bortezomib restrains M2 polarization and reduces CXCL16-associated CXCR6CD4 T cell chemotaxis in bleomycin-induced pulmonary fibrosis.

Background: The development of pulmonary fibrosis involves a cascade of events, in which inflammation mediated by immune cells plays a pivotal role. Chemotherapeutic drugs have been shown to have dual effects on fibrosis, with bleomycin exacerbating pulmonary fibrosis and bortezomib alleviating tissue fibrotic processes. Understanding the intricate interplay between chemotherapeutic drugs, immune responses, and pulmonary fibrosis is likely to serve as the foundation for crafting tailored therapeutic strategies.

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.

Mitochondrial metabolism is essential for invariant natural killer T cell development and function.

Conventional T cell fate and function are determined by coordination between cellular signaling and mitochondrial metabolism. Invariant natural killer T (iNKT) cells are an important subset of "innate-like" T cells that exist in a preactivated effector state, and their dependence on mitochondrial metabolism has not been previously defined genetically or in vivo. Here, we show that mature iNKT cells have reduced mitochondrial respiratory reserve and iNKT cell development was highly sensitive to perturbation of mitochondrial function.

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.

TAGAP instructs Th17 differentiation by bridging Dectin activation to EPHB2 signaling in innate antifungal response.

The TAGAP gene locus has been linked to several infectious diseases or autoimmune diseases, including candidemia and multiple sclerosis. While previous studies have described a role of TAGAP in T cells, much less is known about its function in other cell types. Here we report that TAGAP is required for Dectin-induced anti-fungal signaling and proinflammatory cytokine production in myeloid cells.

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.

CD4 T cell loss and Th2 and Th17 bias are associated with the severity of severe fever with thrombocytopenia syndrome (SFTS).

Severe fever with thrombocytopenia syndrome (SFTS) is a newly emerging infectious disease caused by a novel bunyavirus with high mortality. Immune suppression is thought to be crucial in disease progression. However, data on immune responses during SFTS are scarce.

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).

Crosstalk between type II NKT cells and T cells leads to spontaneous chronic inflammatory liver disease.

Background & Aim: Natural killer T (NKT) cells are CD1d-restricted innate-like T cells that modulate innate and adaptive immune responses. Unlike the well-characterized invariant/type I NKT cells, type II NKT cells with a diverse T cell receptor repertoire are poorly understood. This study defines the pathogenic role of type II NKT cells in the etiology of chronic liver inflammation.

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.

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.

The adaptor protein SAP regulates type II NKT-cell development, cytokine production, and cytotoxicity against lymphoma.

CD1d-restricted NKT cells represent a unique lineage of immunoregulatory T cells that are divided into two groups, type I and type II, based on their TCR usage. Because there are no specific tools to identify type II NKT cells, little is known about their developmental requirements and functional regulation. In our previous study, we showed that signaling lymphocytic activation molecule associated protein (SAP) is essential for the development of type II NKT cells.