Immunologic Research最新文献

Experimental studies of chronic noise exposure in modern urban life testified about oxidative stress due to the corresponding hormones effects leading to accumulation of reactive oxygen species and endothelial dysfunction. This study aims to evaluate the protective effect of α2-adrenoblockers to modulate oxidative stress and corticosterone levels due to chronic noise exposure. To achieve this, we examined the effects of beditin (2-aminothiozolyl-1,4-benzodioxane) and mesedin (2-(2-methyl-amino-thiozolyl)-1,4-benzodioxane hydrochloride), along with changes in corticosterone, Ca2 + content, and morphological alterations in various tissues under noise-induced stress. Beyond this, detection of immune-reactivity and proliferation of Galarmin-containing cells in adrenals, and isolation of the total fractions of superoxide-producing associate from the rat liver under noise exposure and the beditin and mesedin actions on them were pertinent. Experiments were provided on the albino female rats divided into four groups: (1) control, (2) noise-exposed, (3) noise-exposed and beditin-injected (2 mg/kg, i.p.), and (4) noise-exposed and mesedin-injected (10 mg/kg, i.p.) animals. The noise exposure was of 91 dBA noise on 60 days with a daily duration of 8 h. For the first time, the total fractions of superoxide-containing associates were separated from the cell membranes of the rat liver tissue under the chronic noise stress conditions and the regulative effects of the α₂-adrenoblockers. Increased ⁴⁵Ca²⁺ and decreased corticosterone levels in the mentioned tissues, as well as dystrophic changes, were observed under the chronic noise exposure. Prominently, α₂-adrenoblockers showed antioxidant effects, modulating pathological shifts of the noise-induced stress.

Today, in the modern world, allergic diseases, also described as atopic allergies, are classified as a type of multifactorial disorder due to the complex interplay between genetics, environment, and socioeconomic factors that influence the disease's manifestation, severity, and one's predisposition to allergic diseases. It is undeniable that many reported studies have pointed out that the mast cell is one of the leading key players involved in triggering an allergic reaction. To improve our understanding of the molecular and cellular mechanisms underlying allergy, various mast cell lines have been employed in vitro to study the pathogenesis of allergic diseases for the past decades. However, there is no consensus on many fundamental aspects associated with their use, such as the effects of culture media composition and the type of inducer used for cell degranulation. As the standardization of research protocols and disease models is crucial, we present the outcome of a systematic review of scientific articles using three major immortalized in vitro mast cell lines (HMC-1, LAD2, and RBL-2H3) to study allergy. This systematic review described the cell source, culture conditions, inducers used for degranulation, and mediators released for examination. We hope that the present systematic review may help to standardize the use of immortalized in vitro mast cell lines in allergy research and serve as a user's guide to understand the fundamental aspects of allergy as well to develop an effective allergy therapy in the future for the betterment of human good health and wellbeing.

Cytotoxic DNAs, methylation, histones and histones binding proteins are speculated to induce DNA sensors. Under stressed condition, the antigenic patterns, PAMPs and DAMPs, trigger the hyperactive innate response through DNA, DNA-RNA hybrids, oligonucleotides, histones and mtDNA to initiate cGAMP-STING-IFN I cascade. HSV -1&2, HIV, Varicella- Zoster virus, Polyomavirus, Cytomegalovirus, and KSHV negatively regulate the STING-MAVS-TBK-1/1KKE pathway. Implications in STING-PKR-ER regulation often run into causing senescence and organ fibrosis. Post-translational modifications such as, phosphorylation, ubiquitination, SUMOylation, hydrolysis etc. downstream the processing of cGAS-STING that determine the fate of disease prognosis. Self-DNA under normal circumstances is removed through DNase III action; however, its deficiency is the great cause of RA diseases. Regular STING activation in chronic diseases could lead to exacerbate the neurodegenerative disorders due to constant mtDNA leakage. 2' 3' cGAMP or CDN or its associates are being explored as STING agonist therapeutics to treat solid/metastatic tumors to help infiltrate the immune cells, cytokines and chemokines to regulate the protective response. Liposomes, polymer nanoparticles, and cell-derived nanoparticles are also meant to increase the drug efficiency and stability for desired immune response to enhance the IFN I production. This review highlights the implications of cGAMP-STING- IFN I cascade and related pathways involved in the disease prognosis, therapeutics and considering the gaps on different aspects to utilize its greater potential in disease control.

The presence of tertiary lymphoid structures (TLSs) has been correlated with improved prognosis and clinical outcomes in response to immunotherapy in certain solid tumors. However, the precise role of TLSs in lung adenocarcinoma (LUAD) remains unclear. Four datasets of LUAD were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The TLSs model was constructed using a multivariate Cox proportional hazards model. GO and KEGG analyses were performed to explore the biological process associated with the TLSs model. The ESTIMATE and CIBERSORT algorithms were employed to quantify immune infiltration status. TLSs signature genes (TSGs) were identified, including chemokine signature genes, TFH cell markers, TH1 cell and B cell markers, and a plasma cell marker. Diagnostic evaluations identified key genes with high diagnostic value, particularly among chemokine signature genes and TFH cells markers. Furthermore, high expression of CCL20 and IL1R2 was correlated with poorer outcomes, while other TSGs indicated more favorable prognoses. A novel TLSs score model was constructed, integrating 4 TSGs (SGPP2, MS4A1, IL1R2 and CCL20), which accurately predicted patient survival and was independently associated with prognosis. Additionally, the TLSs score served as a robust indicator for LUAD survival prediction, outperforming traditional staging systems. Comprehensive analyses of enriched pathways and immune cell infiltration patterns revealed that this score involved in metabolic processes and immune cell regulation. Furthermore, the TLSs score showed potential as an indicator of response to immunotherapy, with higher scores associated with reduced expression of immune checkpoint genes and poorer response rates. The TLSs score may serve as a predictor of prognosis and immunotherapeutic response in LUAD. These findings may offer new insights on the study of malignancy and personalized immunotherapy for LUAD patients.

Septic arthritis (SA) caused by Staphylococcus aureus is a severe inflammatory joint disease, characterized by synovitis accompanied with cartilage destruction and bone erosion. The available antibiotic treatment alone is insufficient to resolve the inflammation that leads to high rates of morbidity and mortality. Among the CD4⁺ T helper lymphocytes, the Th17 and Tregs are key regulators of immune homeostasis. A high Th17 could lead to autoimmunity, whereas an increase in Tregs indicates immunosuppression. Depending on the external cytokine milieu, naïve CD4⁺ T cells transform into either Th17 or Treg cell lineage. TGF-β in the presence of IL-21 produces Th17 cells and drives the inflammatory cascade of reactions. We studied the effects of in vivo neutralization of TGF-β and IL-21 in septic arthritic mice to control arthritic inflammation, which has not been studied before. The arthritic index showed maximum severity in the SA group which substantially reduced in the Ab-treated groups. Flow cytometric analyses of peripheral blood collected from mice at 9DPI revealed the highest Th17/Treg ratio in the SA group but least in the combined-antibody-treated group. TGF-β1 and IL-21 cytokine production from serum, spleen, and synovial tissue homogenates was significantly reduced in the dual Ab-treated group than in the untreated SA group. From the Western blot analyses obtained from splenic lymphocytes at 9 DPI, we elucidated the possible underlying mechanism of interplay in downstream signalling involving the interaction between different STAT proteins and SOCS, NF-κB, RANKL, mTOR, iNOS, and COX-2 in regulating inflammation and osteoclastogenesis. On endogenous blockade with TGF-β and IL-21, the Th17/Treg ratio and resultant arthritic inflammation in SA were found to be reduced. Therefore, maintaining the Th17/Treg balance is critical to eradicate infection as well as suppress excessive inflammation and neutralization of TGF-β and IL-21 could provide a novel therapeutic strategy to treat staphylococcal SA.

Oxidative stress (OS) injury is pivotal in acute pancreatitis (AP) pathogenesis, contributing to inflammatory cascades. Irisin, a ubiquitous cytokine, exhibits antioxidant properties. However, the role of irisin in AP remains inconclusive. Our study aims to elucidate irisin expression in AP patients and investigate its mechanism of action to propose a novel treatment strategy for AP. Serum irisin levels in 65 AP patients were quantified using an enzyme-linked immunosorbent assay and correlated with disease severity scores. Core genes implicated in AP-related oxidative stress were identified and screened via bioinformatics analysis. The therapeutic efficacy of irisin in AP was confirmed using a murine cerulein-induced AP model. The intrinsic mechanism of irisin's antioxidative stress action was investigated and verified in pancreatic AR42J cells (Supplementary Fig. 1). Common targets shared by irisin and AP were further validated using a molecular docking model which was constructed for virtual docking analysis. This study investigated alterations in redox status in AP and found a significant reduction in serum irisin levels, correlating inversely with AP severity. In a murine AP model, we showed that irisin triggers an antioxidative stress program via the KEAP1 gene; this process helps reestablish redox balance by decreasing the buildup of reactive oxygen species (ROS) and suppressing the secretion of inflammatory mediators within pancreatic tissues Notably, increased KEAP1 expression counteracted the antioxidative effects of irisin. Our findings unveil a novel therapeutic mechanism for AP, wherein irisin inhibits KEAP1 to alleviate OS. Increasing irisin levels in vivo presents a promising strategy for AP treatment.

Recently, a strategy involving the engineering of chemokine receptors on immune cells was developed to optimize adoptive cell therapy (ACT) for solid tumors. Given the variability in chemokine secretion among different tumor types, identifying and modulating the appropriate chemokine receptors is crucial. In this study, we utilized extensive RNA sequencing data from both tumor tissues from The Cancer Genome Atlas and normal tissues from Genotype-Tissue Expression to investigate the expression profiles of chemokines. Through analysis, we identified eight chemokine receptors associated with increased chemokine levels in tumor tissues compared to normal tissues, making them promising candidates for enhancing ACT. Subsequent examination of tumor-infiltrating lymphocytes and chimeric antigen receptor-T cells revealed that five out of the eight candidate chemokine receptors did not exhibit elevated expression in T cells. Among five candidates, we demonstrated that CXCR5 is a particularly promising candidate for enhancing cell migration without compromising cell viability or cytotoxicity. In conclusion, our study underscores the potential of five chemokine receptors (CCR6, CCR9, CXCR1, CXCR5, and XCR1) as valuable targets for modulating ACT to enhance cell trafficking and potentially improve cancer therapy outcomes.

Toll-like receptors (TLRs) are crucial components of innate immunity. A specific form of genetic variation in TLR genes may increase the chance of developing leukemia. The present investigation conducted a comprehensive meta-analysis to examine the correlation between three TLR polymorphisms, namely TLR2 (rs3804099), TLR4 (rs4986790), and TLR9 (rs187084), within the leukemia risk group. An in-depth literature search was performed using Web of Science, PubMed, and Google Scholar to identify noteworthy research published in these scientific databases from 2012 to 2024. Research articles were evaluated according to rigorous inclusion criteria, and data was compiled for meta-analysis using Microsoft Excel (Ver. 2013), MedCalc (Ver. 19.3), and RevMan software (Ver. 5.3). Finally, 11 qualified studies were selected for the ongoing investigation, encompassing a combined total of 1315 leukemia cases and 1340 controls. Using a dominant genotype model, the meta-analysis found that the TLR2 (rs3804099) and TLR9 (rs187084) polymorphisms were strongly linked to higher risk of leukemia, with ORs of 2.042 (95% CI: 1.35-3.08, p = 0.001) and 1.38 (95% CI: 1.14-1.67, p = 0.001) respectively. Notably, the TLR4 (rs4986790) polymorphism did not exhibited any substantial correlation with the incidence of leukemia. The results indicate that variations in TLR2 and TLR9 genes could be considered a novel genetic biomarker for the leukemia development, highlighting their potential use in risk assessment and targeted therapies. This emphasizes the possibility of using these variations in evaluating risk and developing targeted remedies. However, greater research capacities are required to research into the fundamental mechanisms and authenticate these trends in other populations.

In tropical countries, malaria transmission is the major health issue. To eradicate malaria, health communities depend on the control measure that affects economy and environment of the countries. To overcome these burdens, there is a great need to develop vaccine against malaria, but there is no vaccine to control malaria effectively. Transmission blocking vaccine (TBV) is the best alternative approach to control malaria, which inhibits the malaria transmission. Mosquito-based TBVs, blocks the transmission of Plasmodium developmental stages in mosquito. There are some potential candidate antigens for mosquito-based TBV, e.g., AgCPB1, AnAPN1, AgFREP1, etc. AcSGU is one of the most potential candidates for TBVs. AcSGU protein is glycol-anchored protein in Anopheles culicifacies which is highly expressed after blood feeding. In the present study acsgu gene was amplified from genomic DNA, sequenced (GenBank id: MN402758) and characterised. The sequence of acsgu (gene and protein) was analysed by different immuno-informatics tools to confirm its potentiality as a candidate antigen. The target protein was cloned, isolated and immunised for immunogenic response analysis. The acsgu gene is single exonic which encodes for AcSGU protein with single functional MBF2 domain. It is conserved in most of the Anopheles species. Bioinformatics analysis confirmed the stability and immunogenic nature of the protein. Protein-Protein interaction revealed effective interaction of AcSGU with Pf47 and TLR4 molecules. AcSGU protein was expressed in E. coli BL21 (DE3) by using expression vector pLATE51. The immunogenic response in AcSGU protein was remarkable in the rabbit. This study confirmed that AcSGU protein is the potential candidate for transmission blocking vaccine to generate anti-midgut immunity against plasmodium. It can be used as a candidate for the development of multistage targeting vaccines against malaria.

B-cell acute lymphoblastic leukemia (B-ALL) is the most common form of cancer diagnosed in children. While the majority of patients survive with conventional treatment, chemotherapeutic agents have adverse effects and the potential for relapse persists even after full recovery. Given their pivotal function in anti-cancer immunity, there has been a surge in research exploring the potential of natural killer (NK) cells in immunotherapy, which has emerged as a promising avenue for treating leukemia. Nevertheless, the efficacy of NK cell immunotherapy is less pronounced than expected, which suggests the external conditions that affect NK cell functions after the administration to patients with leukemia. In this study, the effects of humoral components in the bone marrow humoral components of B-ALL patients on healthy NK cells were investigated. Healthy peripheral blood mononuclear cells were cultured with and without bone marrow-derived plasma samples of B-ALL patients. The expression of PD-1 and IL-10 were found to be increased whereas the proliferative capacities of NK cells were found to be decreased at the presence of B-ALL plasma samples. Moreover, high IL-10 versus low IL-18 levels were detected in bone marrow plasma samples of B-ALL patients. These findings indicate that humoral components in the bone marrow of B-ALL patients exert a suppressive effect on NK cell functions.