Immunology

Inflammation is initiated and driven by a mixture of mediators, which modify effects of each other. This study analysed in vitro pro-inflammatory activity of inflammatory cytokines (TNFα and IL-1β) in a combination with a lipid DAMP molecule, oxidized palmitoyl-arachidonoyl-phosphatidylcholine (OxPAPC). The study was performed on endothelial and monocytic cell lines. The cells were treated with different concentrations of TNFα or IL-1β, OxPAPC and their combinations, either in the presence or absence of drugs regulating inflammation...

This study longitudinally evaluated the immune response in individuals over a year after receiving three doses of an inactivated SARS-CoV-2 vaccine, focusing on reactions to Omicron breakthrough infections. From 63 blood samples of 37 subjects, results showed that the third booster enhanced the antibody response against Alpha, Beta, and Delta VOCs but was less effective against Omicron. Although antibody titres decreased post-vaccination, SARS-CoV-2-specific T-cell responses, both CD4+ and CD8+ , remained stable...

Hyperactivation of the cyclic-GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signalling pathway has been shown to be associated with the development of a variety of inflammatory diseases, and the discovery of an inhibitor of the cGAS-STING signalling pathway holds great promise in the therapeutic interventions. Epimedium flavonoid (EF), a major active ingredient isolated from the medicinal plant Epimedium, has been reported to have good anti-inflammatory activity, but its exact mechanism of action remains unclear...

In 2015, the oncolytic herpes simplex virus 1 (HSV-1) T-VEC (talimogene laherparepvec) was approved for intratumoral injection in non-resectable malignant melanoma. To determine whether viral replication is required for oncolytic activity, we compared replication-deficient HSV-1 d106S with replication-competent T-VEC. High infectious doses of HSV-1 d106S killed melanoma (n = 10), head-and-neck squamous cell carcinoma (n = 11), and chondrosarcoma cell lines (n = 2) significantly faster than T-VEC as measured by MTT metabolic activity, while low doses of T-VEC were more effective over time...

The aetiology and progression of systemic lupus erythematosus (SLE) resulted from a complex sequence of events generated both from genetic and epigenetic processes. In the current research, the effect of methyl-supplemented nutrition on the development of SLE was studied in the pristane-induced mouse model of the disease. The results clearly demonstrated decreased anti-dsDNA antibody and proteinuria levels, modulation of cytokines and protected renal structures in the group of treated mice. An additional increase in the DNA methylation of mouse B lymphocytes was also observed...

Myocarditis has emerged as a rare but lethal immune checkpoint inhibitor (ICI)-associated toxicity. However, the exact mechanism and the specific therapeutic targets remain underexplored. In this study, we aim to characterise the transcriptomic profiles based on single-cell RNA sequencing from ICI-related myocarditis. Peripheral blood mononuclear cell (PBMC) samples were collected from four groups for single-cell RNA sequencing: (1) patients with newly diagnosed lung squamous cell carcinoma before treatment (Control Group); (2) patients with lung squamous cell carcinoma with PD-1 inhibitor therapy who did not develop myocarditis (PD-1 Group); (3) patients during fulminant ICI-related myocarditis onset (Myocarditis Group); and (4) Patients with fulminant ICI-related myocarditis during disease remission (Recovery Group)...

Vaccination after birth provides protection against pathogen infection and immune related disorders in healthy children. The detailed effects of vaccination on neonatal immunity, however, remain largely unknown. Here, we reported that vaccination using Bacillus Calmette-Guérin (BCG) diminished the immunosuppressive function of myeloid-derived suppressor cells in neonatal mice, an immature myeloid population. A combination of single-cell transcriptome, metabolite profiling, and functional analysis demonstrated that upregulation of mTOR/HIF1a signalling and the enhanced glycolysis explained the effects of BCG on neonatal myeloid cells...

Group 2 innate lymphoid cells (ILC2s) play critical roles in driving the pathogenesis of allergic airway inflammation. The mechanisms underlying the regulation of ILC2s remain to be fully understood. Here, we identified neuropilin-1 (NRP1) as a surface marker of ILC2s in response to IL-33 stimulation. NRP1 was abundantly expressed in ILC2s from lung under steady state, which was significantly reduced upon IL-33 stimulation. ILC2s with high expression of NRP1 (NRP1high ) displayed lower response to IL-33, as compared with NRP1low ILC2s...

Pancreatic cancer (PC) is a highly malignant tumour of the digestive system with poor therapeutic response and low survival rates. Immunotherapy has rapidly developed in recent years and has achieved significant outcomes in numerous malignant neoplasms. However, responses to immunotherapy in PC are rare, and the immunosuppressive and desmoplastic tumour microenvironment (TME) significantly hinders their efficacy in PC. Tumour-associated neutrophils (TANs) play a crucial role in the PC microenvironment and exert a profound influence on PC immunotherapy by establishing a robust stromal shelter and restraining immune cells to assist PC cells in immune escape, which may subvert the current status of PC immunotherapy...

Numerous diseases of the immune system can be traced back to the malfunctioning of the regulatory T cells. The aetiology is unclear. Psychological stress can cause disruption to the immune regulation. The synergistic effects of psychological stress and immune response on immune regulation have yet to be fully understood. The intention of this study is to analyse the interaction between psychological stress and immune responses and how it affects the functional status of type 1 regulatory T (Tr1) cells. In this study, ovalbumin peptide T-cell receptor transgenic mice were utilised...

Natural killer (NK) cell is a valuable tool for immunotherapy in cancer treatment, both the cultured cell line NK92 and primary NK cells are widely studied and used in research and clinical trials. Clinical observations witnessed the improvement of patients' NK cells in terms of cell counts and cytotoxic activity upon dasatinib treatment, an approved drug for chronic myeloid leukaemia and Ph+ acute lymphocytic leukaemia. Several studies supported the clinical observations, yet others argued a detrimental effect of dasatinib on NK cells...

Macrophages expressing group V phospholipase A2 (Pla2g5) release the free fatty acid (FFA) linoleic acid (LA), potentiating lung type 2 inflammation. Although Pla2g5 and LA increase in viral infections, their role remains obscure. We generated Pla2g5flox/flox mice, deleted Pla2g5 by using the Cx3cr1cre transgene, and activated bone marrow-derived macrophages (BM-Macs) with poly:IC, a synthetic double-stranded RNA that triggers a viral-like immune response, known Pla2g5-dependent stimuli (IL-4, LPS + IFNγ, IL-33 + IL-4 + GM-CSF) and poly:IC + LA followed by lipidomic and transcriptomic analysis...

Alterations in airway epithelial homeostasis increase viral respiratory infections risk. Viral infections frequently are associated with chronic obstructive pulmonary disease (COPD) exacerbations, events that dramatically promote disease progression. Mechanism promoting the main respiratory viruses entry and virus-evocated innate and adaptive immune responses have now been elucidated, and an oxidative stress central role in these pathogenic processes has been recognized. Presence of reactive oxygen species in macrophages and other cells allows them to eliminate virus, but its excess alters the balance between innate and adaptive immune responses and proteases/anti-proteases and leads to uncontrolled inflammation, tissue damage, and hypercoagulability...

Myeloid-derived suppressor cells (MDSCs) increase in number and gain immunosuppressive functions in tumours and many other pathological conditions. MDSCs are characterized by their strong T-cell immunosuppressive capacity. The effects that MDSCs may have on B cells, especially within the tumour microenvironment, are less well understood. Here, we report that either monocytic MDSCs or polymorphonuclear MDSCs can promote increases in interleukin (IL)-10-expressing CD19hi FcγRIIbhi regulatory B cells in vitro and in vivo...

Host immune response is key for protection in tuberculosis, but the causative agent, Mycobacterium (M.) tuberculosis, manages to survive despite immune surveillance. Key mechanisms of immune protection have been identified, but the role of immunopathology in the peripheral blood of tuberculosis patients remains unclear. Tuberculosis immunopathology in the blood is characterised by patterns of immunosuppression and hyperinflammation. These seemingly contradictory findings and the pronounced heterogeneity made it difficult to interpret the results from previous studies and to derive implications of immunopathology...

Dendritic cells (DCs) are the most significant antigen presenting cells of the immune system, critical for the activation of naïve T cells. The pathways controlling DC development, maturation, and effector function therefore require precise regulation to allow for an effective induction of adaptive immune response. MYSM1 is a chromatin binding deubiquitinase (DUB) and an activator of gene expression via its catalytic activity for monoubiquitinated histone H2A (H2A-K119ub), which is a highly abundant repressive epigenetic mark...

Natural IgE cytotoxic peptides (nECPs), which are derived from the constant domain of the heavy chain of human IgE producing B cells via endoplasmic reticulum (ER) stress, are decorated onto MHC class 1a molecules (MHCIa) as unique biomarkers for CTL (cytotoxic T lymphocyte)-mediated immune surveillance. Human IgE exhibits only one isotype and lacks polymorphisms; IgE is pivotal in mediating diverse, allergen-specific allergies. Therefore, by disrupting self-IgE tolerance via costimulation, the CTLs induced by nECPs can serve as universal allergy vaccines (UAVs) in humans to dampen IgE production mediated by diverse allergen-specific IgE-secreting B cells and plasma cells expressing surface nECP-MHCIa as targets...

The Beige and Chediak-Higashi (BEACH) domain-containing, Neurobeachin-like 2 (NBEAL2) protein is a molecule with a molecular weight of 300 kDa. Inactivation of NBEAL2 by loss-of-function mutations in humans as well as deletion of the Nbeal2 gene in mice results in functional defects in cells of the innate immune system such as neutrophils, NK-cells, megakaryocytes, platelets and of mast cells (MCs). To investigate the detailed function of NBEAL2 in murine MCs we generated MCs from wild type (wt) and Nbeal2-/- mice, and deleted Nbeal2 by CRISPR/Cas9 technology in the murine mast cell line MC/9...

Immune system imbalances contribute to the pathogenesis of several different diseases, and immunotherapy shows great therapeutic efficacy against tumours and infectious diseases with immune-mediated derivations. In recent years, molecules targeting the programmed cell death protein 1 (PD-1) immune checkpoint have attracted much attention, and related signalling pathways have been studied clearly. At present, several inhibitors and antibodies targeting PD-1 have been utilized as anti-tumour therapies. However, increasing evidence indicates that PD-1 blockade also has different degrees of adverse side effects, and these new explorations into the therapeutic safety of PD-1 inhibitors contribute to the emerging concept that immune normalization, rather than immune enhancement, is the ultimate goal of disease treatment...

Currently lacking research to explore the correlation between inflammatory markers and the efficacy of immune checkpoint inhibitors (ICIs) combined with chemotherapy in the treatment of advanced gastric cancer. This study is a retrospective study and included patients with advanced gastric cancer who receiving ICIs combined with chemotherapy from January 2020 to December 2022. We analysed the relationship between systemic inflammatory markers and the efficacy of ICIs combined chemotherapy and constructed a clinical prediction model...