Immunology

Tumorigenesis entails circumventing cell-intrinsic regulatory mechanisms while avoiding extrinsic immune surveillance and other host defence systems. Nevertheless, how tumour cells' ability to eliminate misfolded proteins affects immune surveillance remains poorly understood. In this study, we find that overexpression of murine tripartite motif-containing protein 30a (TRIM30a) sensitises tumour cells to natural killer (NK) cells-mediated cytolysis. TRIM30a has no effect on tumour cell proliferation or apoptosis in vitro...

NLR family pyrin domain containing 2 (NLRP2) is a novel member of the Nod-like receptor (NLR) family. However, our understanding of NLRP2 has long been ambiguous. NLRP2 may have a role in the innate immune response, but its 'specific' functions remain controversial. Although NLRP2 can initiate inflammasome and promote inflammation, it can also downregulate inflammatory signals. Additionally, NLRP2 has been reported to function in the reproductive system and shows high expression in the placenta. However, the exact role of NLRP2 in the reproductive system is unclear...

We previously reported that patients with multidrug-resistant tuberculosis (MDR-TB) showed low systemic and Mtb-induced Th22 responses associated to high sputum bacillary load and severe lung lesions suggesting that Th22 response could influence the ability of these patients to control bacillary growth and tissue damage. In MDR-TB patients, the percentage of IL-22+ cells inversely correlates with the proportion of senescent PD-1+ T cells. Herein, we aimed to evaluate the pathways involved on the regulation of systemic and Mtb-induced Th22 response in MDR-TB and fully drug-susceptible TB patients (S-TB) and healthy donors...

Nipah virus (NiV) causes severe encephalitis in humans. Three NiV strains NiV-Malaysia (NiVM ), NiV Bangladesh (NiVB ), and NiV India (NiVI reported in 2019) have been circulating in South-Asian nations. Sporadic outbreak observed in South-East Asian countries but human to human transmission raises the concern about its pandemic potential. The presence of the viral genome in reservoir bats has further confirmed that NiV has spread to the African and Australian continents. NiV research activities have gained momentum to achieve specific preparedness goals to meet any future emergency-as a result, several potential vaccine candidates have been developed and tested in a variety of animal models...

On the basis of the mechanisms of action and characteristics of immune effects, immunity is commonly categorized into innate and adaptive immunity. Adaptive immunity is associated with the response to non-self-entities and is characterized by high specificity and memory properties. In contrast, innate immunity has traditionally been considered devoid of memory characteristics. However, an increasing number of studies have sought to challenge this conventional immunological dogma and shown that innate immune cells exhibit a more robust and rapid response to secondary stimulation, thus providing evidence of the immunological memory in innate immunity...

Previous studies have demonstrated that T cell exhaustion is associated with poor clearance of Hepatitis B virus (HBV). However, whether the expression of exhaustion markers on innate-like circulating γδ T cells derived from patients with HBV infection correlates with the serum level of vitamin D is not completely understood. In this study, we found that the frequency of circulating Vδ2+ T cell and serum levels of vitamin 25(OH)D3 were significantly decreased in patients with HBV. And serum 25(OH)D3 levels in HBV-infected patients were negatively correlated with HBV DNA load and PD-1 expression on γδ T cells...

Rheumatoid arthritis is a chronic and systemic inflammatory disease that affects approximately 1% of the world's population and is characterised by joint inflammation, the destruction of articular cartilage and bone, and many potentially life-threatening extraarticular manifestations. B lymphocytes play a central role in the pathology of rheumatoid arthritis as the precursors of autoantibody secreting plasma cells, as highly potent antigen-presenting cells, and as a source of various inflammatory cytokines, however, the effects of rheumatoid arthritis on B lymphocyte development remain poorly understood...

Sepsis is a life-threatening disease characterized by multiple organ dysfunction. B cells play a pivotal role in sepsis. Here, we first observed the significantly reduced Flot2 gene expression in B cells from patients with bacterial sepsis and endotoxin-induced septic mice. However, the effects of Flot2 on sepsis and B-cell immunity remain unknown. Thus, we sorted B cells from Flot2 knockout (Flot2-/- ) mice, RNA-seq revealed significantly upregulated effector B cell (Beff) cytokines such as Il6, Il1b and Cxcl10 after Flot2 deficiency, while it showed no effect on the expression of regulatory B cell (Breg) cytokines such as Il10, Tgfb...

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Adoptive regulatory T-cell (Treg) transfer has emerged as a promising therapeutic strategy for regulating immune responses in organ transplantation, graft versus host disease, and autoimmunity, including Type 1 diabetes. Traditionally, Treg for adoptive therapy have been sorted and expanded in vitro using high doses of IL-2, demonstrating stability and suppressive capabilities. However, limitations in their long-term survival post-infusion into patients have been observed. To address this challenge, we investigated a novel expansion protocol incorporating interleukin-7 (IL-7) alongside the traditional method utilizing IL-2 (referred to as IL-7 method, IL-7M)...

Bronchial asthma is a heterogeneous disease characterised by chronic airway inflammation. A variety of immune cells such as eosinophils, mast cells, T lymphocytes, neutrophils and airway epithelial cells are involved in the airway inflammation and airway hyperresponsiveness in asthma pathogenesis, resulting in extensive and variable reversible expiratory airflow limitation. However, the precise molecular mechanisms underlying the allergic immune responses, particularly immunometabolism, remains unclear. Studies have detected enhanced oxidative stress, and abnormal metabolic progresses of glycolysis, fatty acid and amino acid in various immune cells, inducing dysregulation of innate and adaptive immune responses in asthma pathogenesis...

Skp2 plays multiple roles in malignant tumours. Here, we revealed that Skp2 negatively regulates type-I interferon (IFN-I)-mediated antiviral activity. We first noticed that Skp2 can promote virus infection in cells. Further studies demonstrated that Skp2 interacts with IFN-I receptor 2 (IFNAR2) and promotes K48-linked polyubiquitination of IFNAR2, which accelerates the degradation of IFNAR2 proteins. Skp2-mediated downregulation of IFNAR2 levels inhibits IFN-I signalling and IFN-I-induced antiviral activity...

Under perturbing conditions such as infection with Leishmania, a protozoan parasite living within the phagosomes in mammalian macrophages, cellular and organellar structures, and metabolism are dynamically regulated for neutralizing the pressure of parasitism. However, how modulations of the host cell metabolic pathways support Leishmania infection remains unknown. Herein, we report that lipid accumulation heightens the susceptibility of mice to L. donovani infection and promotes resistance to first-line anti-leishmanial drugs...

The SARS-CoV-2 (COVID-19) virus has caused a devastating global pandemic of respiratory illness. To understand viral pathogenesis, methods are available for studying dissociated cells in blood, nasal samples, bronchoalveolar lavage fluid and similar, but a robust platform for deep tissue characterization of molecular and cellular responses to virus infection in the lungs is still lacking. We developed an innovative spatial multi-omics platform to investigate COVID-19-infected lung tissues. Five tissue-profiling technologies were combined by a novel computational mapping methodology to comprehensively characterize and compare the transcriptome and targeted proteome of virus infected and uninfected tissues...

Inflammatory bowel disease (IBD) is a chronic gastrointestinal inflammatory disease associated with CD4+ Th1 and Th17 cell immune responses. Tumour necrosis factor-associated factor 5 (TRAF5) deficiency has been shown to aggravate DSS-induced colitis. However, the potential role of TRAF5 in regulating CD4+ T cell immune responses in the pathogenesis of IBD remains unclear. TRAF5-/- CD4+ CD45RBhigh T cells and WT CD4+ CD45RBhigh T cells were transferred to Rag2-/- mice via intravenous (i.v.) tail injection, respectively, to establish a chronic colitis model...

Phosphoinositide 3-kinase (PI3K) p110δ signalling negatively regulates the production of mouse IgE. However, there are disparities between the mouse and human IgE biology, and the role of PI3K p110δ in the production of human IgE is yet to be determined. To investigate the effect of PI3K p110δ inhibition in the production of human IgE we isolated human B cells from tonsil tissue and stimulated them with IL-4 and anti-CD40 antibody to induce class switching to IgE and IgG1 in the presence or absence of IC87114, a small molecule inhibitor of PI3K p110δ...

A substantial number of colon cancer patients do not benefit from immunotherapy using programmed cell death 1 (PD1) antibodies. Therefore, combination therapy drugs are required to improve the efficacy of colon cancer immunotherapy. Recent studies have shown that deubiquitinases are negative regulators of anti-tumour immunity. In the present study, we investigated the effect of the deubiquitinase inhibitor PR-619 in combination with anti-PD1 for the treatment of colorectal cancer. The results revealed that co-treatment with PR-619 and anti-PD1 significantly inhibited tumour growth in tumour-bearing BALB/c mice compared to monotherapy with a single drug...

It is well known that chimeric antigen receptor T-cell immunotherapy (CAR-T-cell immunotherapy) has excellent therapeutic effect in haematological tumours, but it still faces great challenges in solid tumours, including inefficient T-cell tumour infiltration and poor functional persistence. Flap structure-specific endonuclease 1 (FEN1), highly expressed in a variety of cancer cells, plays an important role in both DNA replication and repair. Previous studies have reported that FEN1 inhibition is an effective strategy for cancer treatment...

The dysfunction of regulatory T cell (Treg) is associated with the pathogenesis of many immune diseases. The regiments used to re-establish Treg's function are currently unsatisfactory and need to be improved. The purpose of this study is to elucidate the synergistic effects of cortisol and endoplasmic reticulum (ER) stress on impairing regulatory T cell functions. In this study, blood samples were collected from patients with food allergy (FA). Immune cells were purified from blood specimens by flow cytometry...

Targeting programmed death 1(PD-1) has been approved for relapsed cervical cancer with unsatisfactory clinical efficacy. This study aims to analyse the impact of PI3K pathway activation on tumour immune microenvironment and evaluates the immune sensitization effect by PI3K inhibition in cervical cancer. The effect of PIK3CA mutation on PD-L1 expression and CD8+ T cells differentiation was determined in cervical cancer tissues. Luciferase and ChIP-qPCR/PCR assays were used to determine the transcriptional regulation of PD-L1 by PIK3CA-E545K...