Immune Function Research Articles

MUC5B regulates alterations in the immune microenvironment in nasopharyngeal carcinoma via the Wnt/β-catenin signaling pathway

ObjectiveTo screen potential differentially expressed genes related to immune function in nasopharyngeal carcinoma through an online database, and to verify their mechanism of action, so as to provide a reference for the diagnosis and treatment of nasopharyngeal carcinoma in the future.MethodsDifferentially expressed genes were analyzed from the GSE227541 dataset, and functional enrichment analysis was conducted. With mucin 5B, oligomeric mucus/gel-forming as the focus, the correlation between its expression and immune indexes was analyzed by using the TIMER database. The expressions of mucin 5B, oligomeric mucus/gel-forming in clinical NPC tissues and adjacent tissue samples were detected Furthermore, mucin 5B, oligomeric mucus/gel-forming abnormal expression vectors were constructed and transfected into human NPC cell CNE-2Z to detect alterations in cell activity, ferroptosis and the immune microenvironment. In addition, the role of the Wnt/β-catenin signaling pathway in nasopharyngeal carcinoma was observed, and the influence of mucin 5B, oligomeric mucus/gel-forming on this pathway was discussed.ResultsA total of 42 differentially expressed genes were found in the GSE227541 dataset, among which mucin 5B, oligomeric mucus/gel-forming was obviously at the core of the entire network. In nasopharyngeal carcinoma tissues, the research team observed the upregulated expression of mucin 5B, oligomeric mucus/gel-forming (P < 0.05). In vitro, increased expression of elevated mucin 5B, oligomeric mucus/gel-forming activates nasopharyngeal carcinoma cell activity and immune escape and inhibits ferroptosis. In terms of pathways, upregulating mucin 5B, oligomeric mucus/gel-forming expression could activate the Wnt/β-catenin pathway.ConclusionsMucin 5B, oligomeric mucus/gel-forming regulates the immune escape of nasopharyngeal carcinoma cells and participates in tumor progression by mediating the Wnt/β-catenin signaling pathway.

Glucose Metabolism Reprogramming of Immune Cells in the Microenvironment of Pancreatic and Hepatobiliary Cancers.

Pancreatic and hepatobiliary cancers are increasing in prevalence and contribute significantly to cancer-related mortality worldwide. Emerging therapeutic approaches, particularly immunotherapy, are gaining attention for their potential to harness the patient's immune system to combat these tumors. Understanding the role of immune cells in the tumor microenvironment (TME) and their metabolic reprogramming is key to developing more effective treatment strategies. This review aims to explore the relationship between immune cell function and glucose metabolism in the TME of pancreatic and hepatobiliary cancers. This review synthesizes current research on the metabolic adaptations of immune cells, specifically focusing on glucose metabolism within the TME of pancreatic and hepatobiliary cancers. We examine the mechanisms by which immune cells influence tumor progression through metabolic reprogramming and how these interactions can be targeted for therapeutic purposes. Immune cells in the TME undergo significant metabolic changes, with glucose metabolism playing a central role in modulating immune responses. These metabolic shifts not only affect immune cell function but also influence tumor behavior and progression. The unique metabolic features of immune cells in pancreatic and hepatobiliary cancers provide new opportunities for targeting immune responses to combat these malignancies more effectively. Understanding the complex relationship between immune cell glucose metabolism and tumor progression in the TME of pancreatic and hepatobiliary cancers offers promising therapeutic strategies. By modulating immune responses through targeted metabolic interventions, it may be possible to improve the efficacy of immunotherapies and better combat these aggressive cancers.

Effects of combined Bacillus coagulans and Yeast fermentation culture on growth performance, plasma biochemical indices, intestinal morphology and microbial of broilers.

The favorable impacts of Bacillus coagulans or Yeast culture on broiler production performance and immune function have been acknowledged. However, the effects of the combined of them (BcYc) on the broilers remained unknown. Thus, the current research aimed to assess the effects of BcYc (at dosages of 0, 200, 300, and 400mg/kg) on growth performance, plasma biochemical indices, antioxidant capacity, and intestinal morphology and microbial composition in broilers. The results revealed that ①broilers receiving 300 and 400mg/kg of BcYc showed significantly higher body weights than the control group at 4d and 21d (P < 0.05). Additionally, when contrasted with the control group, the feed conversion ratio was significantly decreased in 300mg/kg group during 4 to 21d and in 400mg/kg group during 4 to 42d (P < 0.05). ②At 21d, the broilers supplemented with 300 and 400mg/kg of BcYc demonstrated significantly elevated levels of albumin (ALB), glutathione peroxidase activity (GSH-Px), total antioxidant capacity, and catalase activity than the group that not supplemented with BcYc (P < 0.05). At 42d, 400mg/kg group showed significantly higher ALB and total protein, and lower glutamic-pyruvic transaminase activity and malondialdehyde content in contrast to the control group (P < 0.05). Furthermore, at 42d, GSH-Px activity in all experimental groups showed significantly higher compared to the control group (P < 0.05). ③Nevertheless, no significant variation was observed neither in jejunum or duodenum morphology among all groups (P > 0.05). ④Adding 400mg/kg of BcYc led to a significantly higher Sobs index and a lower Simpson index (P < 0.05), and an extremely significantly raised in Shannon index (P < 0.01), while adding 300mg/kg of BcYc led to a significantly enhanced in Shannon index (P < 0.05). Additionally, supplementary BcYc significantly elevated the abundance of Firmicutes in phylum level, and Clostridia, Ruminococcus, Rikenella, Butyricicoccus and Eubacterium in genus level (P < 0.05). To sum up, supplementing BcYc at dosages of 400mg/kg to yellow-feathered broilers diet can help improve the growth performance, regulate plasma biochemical indicators, increase antioxidant capacity, and improve gut community composition.

Zinc Deficiency Reduces Intestinal Secretory Immunoglobulin A and Induces Inflammatory Responses via the Gut-Liver Axis.

Nutritional zinc (Zn) deficiency could impair immune function and affect bowel conditions. However, the mechanism by which Zn deficiency affects the immune function of gut-associated lymphoid tissue (GALT) remains unclear. We investigated how Zn deficiency affects the function of GALT and level of secretory IgA (sIgA), a key component of the intestinal immune barrier, its underlying mechanisms, and whether Zn deficiency induces bacterial translocation to the liver. As previous research has indicated that interleukin (IL)-4 administration or Zn supplementation has a beneficial effect on the spleen of Zn-deficient rats, we investigated whether these supplements reverse the GALT immune system. Five-week-old male rats were fed a standard diet, Zn-deficient diet supplemented with saline or IL-4 for 6 weeks, or Zn-deficient diet followed by a standard diet for 4 weeks. Zn deficiency suppressed sIgA secretion in the intestinal tract by affecting GALT function and induced inflammatory responses through bacterial translocation to the liver via the portal vein. Furthermore, IL-4 administration and Zn supplementation in rats with Zn deficiency elicited comparable beneficial effects on GALT function, suggesting that the administration of either IL-4 or Zn could prevent inflammatory response via bacterial translocation to the liver.

Effects of Different Levels of Lycium barbarum Flavonoids on Growth Performance, Immunity, Intestinal Barrier and Antioxidant Capacity of Meat Ducks.

Background: In vitro findings on the biological functions of Lycium barbarum flavonoids (LBFs) as feed additives are limited. This study aimed to explore the effects of different concentrations of LBFs on the growth performance, immune function, intestinal barrier, and antioxidant capacity of meat ducks. A total of 240 one-day-old male meat ducks were randomly allocated to four groups, each receiving a basal diet supplemented with 0 (control), 250, 500, or 1000 mg/kg of LBFs for 42 d. Results: The results showed that dietary supplementation with 500 mg/kg of LBFs resulted in a significant increase in average daily feed intake, body weight, average daily gain, and feed conversion ratio. Dietary supplementation with 500 or 1000 mg/kg of LBFs resulted in significant decreases in serum levels of D-lactic acid and lipopolysaccharide. Dietary supplementation with 500 mg/kg LBFs significantly decreased diamine oxidase activity and enhanced the activities of catalase, total antioxidant capacity, and glutathione peroxidase in the jejunal mucosa, as well as the activity of total superoxide dismutase and the content of glutathione in the ileal mucosa, while significantly lowering the content of malondialdehyde in the ileal mucosa. Dietary supplementation with 500 mg/kg LBFs significantly up-regulated the mRNA expression of genes associated with intestinal barrier function and antioxidant capacity in the jejunal and ileal mucosa, as well as the protein expression of these antioxidant genes, and led to a significant reduction in the mRNA expression of pro-apoptotic and inflammatory-related genes. Conclusions: The addition of LBFs to the diet improved the growth performance, intestinal barrier function, immune response, and antioxidant capacity of the ducks, which may be closely associated with the activation of the Nrf2 signaling pathway and the inhibition of the NF-κB signaling pathway. The optimal dietary inclusion level of LBFs in ducks was 500 mg/kg.

Bactericidal/Permeability-Increasing Protein (BPI), a Novel Antimicrobial Molecule in Human Breast Milk with Immune Potential.

Breast milk is a fluid of vital importance during the first stages of life of the newborn since, in addition to providing nutrients, it also contains cells and molecules of the immune system, which protect the neonate from infection and, at the same time, modulate the establishment of the microbiota. Bactericidal/permeability-increasing protein (BPI) is relevant in preventing disease and sepsis in neonates. Therefore, the following work aimed to demonstrate the presence of BPI in the different stages of breast milk and its possible immune functions. Our results demonstrate for the first time the presence of soluble BPI and leukocytes and epithelial cells containing it, primarily in the colostrum stage. Using BPI at concentrations typical of colostrum, we observed that it reduces the growth of two distinct E. coli strains, enhances the uptake of these bacteria by monocytes, and suppresses the secretion of the proinflammatory cytokine interleukin (IL)-8 in infected intestinal cells. These findings suggest that BPI transferred via colostrum from mother to newborn may play a significant role in providing antimicrobial and anti-inflammatory protection during the early stages of life.

Gut Microbiota and Diabetes: Pioneering New Treatment Frontiers.

Diabetes Mellitus (DM) is a complex metabolic disorder characterized by chronic hyperglycemia and poses significant global health challenges. Conventional treatments, such as insulin therapy and lifestyle modifications, have shown limited efficacy in addressing the multifactorial nature of DM. Emerging evidence suggests that gut microbiota, a diverse community of microorganisms critical for metabolism and immune function, plays a pivotal role in metabolic health. Dysbiosis, an imbalance in gut microbiota composition, has been linked to insulin resistance, obesity, and DM. Gut microbiota influences glucose metabolism through mechanisms, including short-chain fatty acid production, gut permeability regulation, and immune system interactions, indicating a bidirectional relationship between microbial health and metabolism. Clinical and experimental studies demonstrate that modulating gut microbiota through dietary interventions (prebiotics, probiotics, synbiotics) improves glycemic control and insulin sensitivity in DM patients. Fecal Microbiota Transplantation (FMT) has also shown promise in restoring healthy gut microbiota and alleviating DM-related metabolic disturbances. However, challenges remain, including the need for personalized treatments due to individual microbiota variability and the unknown long-term effects of these interventions. Future research should focus on elucidating the mechanisms by which gut microbiota influences metabolism and refining personalized approaches to enhance DM management.

Protocol for investigating intracellular microbial diversity using single-cell RNA-seq in immune cells of SARS-CoV-2-positive and recovered patients.

Intracellular microorganisms like viruses and bacteria impact immune cell function. However, detection of these microbes is challenging as the majority exist in a non-culturable state. This protocol presents detailed steps to investigate intracellular microbial diversity using single-cell RNA sequencing (scRNA-seq) in immune-cells of SARS-CoV-2-positive and recovered patients. We present a workflow from sample collection to library preparation, covering peripheral blood mononuclear cell (PBMC) isolation, single-cell labeling, cartridge priming, and cell lysis. We outline the steps for analyzing the scRNA-seq data, from data quality control (QC) to detection of intracellular microbes. For complete details on the use and execution of this protocol, please refer to Yadav etal.1.

Butyrate Supplementation Improves Intestinal Health and Growth Performance in Livestock: A Review.

Butyrate supplementation has gained considerable attention for its potential benefits in livestock, particularly concerning intestinal health and growth performance. This review synthesizes recent research on the diverse roles of butyrate, across various livestock species. As a short-chain fatty acid, butyrate is known for enhancing intestinal development, improving immune function, and modulating microbial diversity. Studies indicate that butyrate supports gut barrier integrity, reduces inflammation, and optimizes feed efficiency, especially during the critical weaning and post-weaning periods in calves, piglets, and lambs. Supplementation with butyrate in livestock has been shown to increase average daily gain (ADG), improve gut microbiota balance, promote growth, enhance gut health, boost antioxidant capacity, and reduce diarrhea. Additionally, butyrate plays a role in the epigenetic regulation of gene expression through histone acetylation, influencing tissue development and immune modulation. Its anti-inflammatory and antioxidant effects have been demonstrated across various species, positioning butyrate as a potential therapeutic agent in animal nutrition. This review suggests that optimizing butyrate supplementation strategies to meet the specific needs of each species may yield additional benefits, establishing butyrate as an important dietary additive for enhancing growth performance and health in livestock.

Pretreatment of Palm Kernel Cake by Enzyme-Bacteria and Its Effects on Growth Performance in Broilers.

This study aimed to improve palm kernel cake by reducing anti-nutritional factors with enzymes and enhancing its nutritional value through microbial fermentation. It also examined the effects of these treatments on palm kernel cake in broiler chicken diets. Palm kernel cake was hydrolyzed using xylanase and mannanase under various conditions. Co-fermentation with Lactobacillus plantarum QZSL and Saccharomyces boulardii mafic-1701 was assessed under different parameters. In the animal experiment, 350 male Cobb broiler chicks were divided into seven groups: a control group provided a corn-soybean meal diet, and groups provided diets containing 10% and 20% palm kernel cake, enzyme-hydrolyzed palm kernel cake, and bacteria-enzyme co-fermented palm kernel cake. Optimal conditions for enzymatic hydrolysis of palm kernel cake are 55 °C, pH 3.0, and a 1:2.5 feed-to-water ratio. Adding 0.1 g xylanase and 1.0 g mannanase to 10 g palm kernel cake for 12 h increased reduced sugar content to 139.33 mg/g and reduced neutral detergent fiber to 43.92%. For solid-state fermentation with Lactobacillus plantarum QZSL and Saccharomyces boulardii mafic-1701, optimal conditions are 37 °C, 5% inoculation, 20% moisture, 3 days fermentation, and a 7:3 bacterial ratio. Animal experiments showed significant improvements in broilers' growth, nutrient digestibility, antioxidant capacity, immune function, and intestinal health. Enzyme-bacteria co-fermentation of palm kernel cake boosts its nutritional value and enhances broiler intestinal health.

Molecular profiling of frontal and occipital subcortical white matter hyperintensities in Alzheimer's disease.

White matter hyperintensities (WMHs) are commonly detected on T2-weighted magnetic resonance imaging (MRI) scans, occurring in both typical aging and Alzheimer's disease (AD). Despite their frequent appearance and their association with cognitive decline in AD, the molecular factors contributing to WMHs remain unclear. In this study, we investigated the transcriptomic profiles of two commonly affected brain regions with coincident AD pathology-frontal subcortical white matter (frontal-WM) and occipital subcortical white matter (occipital-WM)-and compared with age-matched cognitively intact controls. Through RNA-sequencing in frontal- and occipital-WM bulk tissues, we identified an upregulation of genes associated with brain vasculature function in AD white matter. To further elucidate vasculature-specific transcriptomic features, we performed RNA-seq analysis on blood vessels isolated from these white matter regions, which revealed an upregulation of genes related to protein folding pathways. Finally, comparing gene expression profiles between AD individuals with high- versus low-WMH burden showed an increased expression of pathways associated with immune function. Taken together, our study characterizes the diverse molecular profiles of white matter changes in AD and provides mechanistic insights into the processes underlying AD-related WMHs.

Role of tertiary lymphoid structures and B cells in clinical immunotherapy of gastric cancer.

Gastric cancer is a common malignant tumor of the digestive tract, and its treatment remains a significant challenge. In recent years, the role of various immune cells in the tumor microenvironment in cancer progression and treatment has gained increasing attention. Immunotherapy, primarily based on immune checkpoint inhibitors, has notably improved the prognosis of patients with gastric cancer; however, challenges regarding therapeutic efficacy persist. Histological features within the tumor microenvironment, such as tertiary lymphoid structures (TLSs), tumor-infiltrating lymphocytes, and the proportion of intratumoral stroma, are emerging as potentially effective prognostic factors. In gastric cancer, TLSs may serve as local immune hubs, enhancing the ability of immune cells to interact with and recognize tumor antigens, which is closely linked to the effectiveness of immunotherapy and improved survival rates in patients. However, the specific cell type driving TLS formation in tumors has not yet been elucidated. Mature TLSs are B-cell regions containing germinal centers. During germinal center formation, B cells undergo transformations to become mature cells with immune function, exerting anti-tumor effects. Therefore, targeting B cells within TLSs could provide new avenues for gastric cancer immunotherapy. This review, combined with current research on TLSs and B cells in gastric cancer, elaborates on the relationship between TLSs and B cells in the prognosis and immunotherapy of patients with gastric cancer, aiming to provide effective guidance for precise immunotherapy.

Sex hormones and allergies: exploring the gender differences in immune responses.

Allergies are closely associated with sex-related hormonal variations that influence immune function, leading to distinct symptom profiles. Similar sex-based differences are observed in other immune disorders, such as autoimmune diseases. In allergies, women exhibit a higher prevalence of atopic conditions, such as allergic asthma and eczema, in comparison to men. However, age-related changes play a significant role because men have a higher incidence of allergies until puberty, and then comes a switch ratio of prevalence and severity in women. Investigations into the mechanisms of how the hormones influence the development of these diseases are crucial to understanding the molecular, cellular, and pathological aspects. Sex hormones control the reproductive system and have several immuno-modulatory effects affecting immune cells, including T and B cell development, antibody production, lymphoid organ size, and lymphocyte death. Moreover, studies have suggested that female sex hormones amplify memory immune responses, which may lead to an excessive immune response impacting the pathogenesis, airway hyperresponsiveness, inflammation of airways, and mucus production of allergic diseases. The evidence suggests that estrogens enhance immune humoral responses, autoimmunity, mast cell reactivity, and delayed IV allergic reactions, while androgens, progesterone, and glucocorticoids suppress them. This review explores the relationship between sex hormones and allergies, including epidemiological data, experimental findings, and insights from animal models. We discuss the general properties of these hormones, their effects on allergic processes, and clinical observations and therapeutic results. Finally, we describe hypersensitivity reactions to these hormones.

Human milk oligosaccharides: bridging the gap in intestinal microbiota between mothers and infants.

Breast milk is an essential source of infant nutrition. It is also a vital determinant of the structure and function of the infant intestinal microbial community, and it connects the mother and infant intestinal microbiota. Human milk oligosaccharides (HMOs) are a critical component in breast milk. HMOs can reach the baby's colon entirely from milk and become a fermentable substrate for some intestinal microorganisms. HMOs can enhance intestinal mucosal barrier function and affect the intestinal function of the host through immune function, which has a therapeutic effect on specific infant intestinal diseases, such as necrotizing enterocolitis. In addition, changes in infant intestinal microbiota can reflect the maternal intestinal microbiota. HMOs are a link between the maternal intestinal microbiota and infant intestinal microbiota. HMOs affect the intestinal microbiota of infants and are related to the maternal milk microbiota. Through breastfeeding, maternal microbiota and HMOs jointly affect infant intestinal bacteria. Therefore, HMOs positively influence the establishment and balance of the infant microbial community, which is vital to ensure infant intestinal function. Therefore, HMOs can be used as a supplement and alternative therapy for infant intestinal diseases.

Age-associated alterations in immune and inflammatory responses in captive olive baboons (Papio anubis).

Advanced age is a primary risk factor for many chronic diseases and conditions; however, age-related immune dysregulation is not well understood. Animal models, particularly those that resemble human age-related physiological changes, are needed to better understand immunosenescence and to improve health outcomes. Here, we explore the utility of the olive baboon (Papio anubis) in studying age-related changes to the immune system and understanding mechanisms of immunosenescence. We examined immune cell, inflammatory responses, cytokines, and cortisol levels using hematology and flow cytometry, mitogen stimulation, multiplex cytokine assay, and cortisol immunoassay. Our results reveal significant age effects on numerous immune and inflammatory responses. For instance, adult and aged monkeys exhibited significantly fewer monocytes than young monkeys. After stimulation with Con A and PWM (separately), we found that old baboons had higher INFγ expression compared to young baboons. Similarly, after stimulation with LPS and PWM (separately), we found that old baboons had higher TNFα expression compared to young baboons. These findings suggest that the olive baboon is a suitable model for biogerontology research, immune senescence, and development of vaccines. Though there are phenotypic and functional similarities between baboons and humans, specific differences exist in immune cell expression and immune function of lymphocytes that should be considered for better experimental outcomes in the development of therapeutics and restoring innate and adaptive immune function in aged individuals.

Metabolic Signaling in the Tumor Microenvironment.

Cancer cells must reprogram their metabolism to sustain rapid growth. This is accomplished in part by switching to aerobic glycolysis, uncoupling glucose from mitochondrial metabolism, and performing anaplerosis via alternative carbon sources to replenish intermediates of the tricarboxylic acid (TCA) cycle and sustain oxidative phosphorylation (OXPHOS). While this metabolic program produces adequate biosynthetic intermediates, reducing agents, ATP, and epigenetic remodeling cofactors necessary to sustain growth, it also produces large amounts of byproducts that can generate a hostile tumor microenvironment (TME) characterized by low pH, redox stress, and poor oxygenation. In recent years, the focus of cancer metabolic research has shifted from the regulation and utilization of cancer cell-intrinsic pathways to studying how the metabolic landscape of the tumor affects the anti-tumor immune response. Recent discoveries point to the role that secreted metabolites within the TME play in crosstalk between tumor cell types to promote tumorigenesis and hinder the anti-tumor immune response. In this review, we will explore how crosstalk between metabolites of cancer cells, immune cells, and stromal cells drives tumorigenesis and what effects the competition for resources and metabolic crosstalk has on immune cell function.

Metabolomics analysis of anaphylactoid reactions induced by Xueshuantong injection in normal and immunocompromised mice.

Xueshuantong injection (Lyophilized) (XSTI) is widely used to treat cardiovascular and cerebrovascular diseases. However, anaphylactoid reactions (ARs) are frequently reported as one of its side effects, and the mechanisms of ARs and their relationship with the different immune status are still not well understood. This article aims to examine the sensitizing effect of XSTI, explore the impact of normal and immunocompromised states on ARs, and analyze AR-related metabolic pathways by metabolomics. An immunocompromised mouse model was established through intraperitoneal injection of cyclophosphamide (CTX). Normal and immunocompromised mice were then treated with normal saline (NS), histamine (HIS), and XSTI, respectively. Behavioral responses, auricle blue staining, and Evans blue (EB) exudation were used as indices to evaluate the sensitization of XSTI on both normal and immunocompromised mice. Subsequently, ARs models with different immune statuses were established, and validated by measuring four serum indicators using enzyme-linked immunosorbent assay (ELISA). Finally, LC-MS metabolomics analysis was performed on mouse serum to evaluate the metabolic pathways. The intensity of ARs induced by XSTI in mice was found to increase with the administered dose, with normal mice exhibiting higher AR intensities compared to immunocompromised mice. Metabolomic analysis revealed significant metabolic changes in XSTI-treated mice. The metabolic pathways predicted from these different metabolites include biotin metabolism, histidine metabolism, glycerolipid metabolism, bile secretion, arachidonic acid metabolism, sphingolipid metabolism, niacin and nicotinamide metabolism, tryptophan metabolism, steroid biosynthesis, and arginine and proline metabolism. Research indicated that the sensitization of XSTI is dose-dependent, and mice with weakened immune functions exhibit lower sensitivity. Through metabolomics research, the differential metabolites in mice were analyzed, and the metabolic pathways inducing ARs were predicted. This study offers guidance on safe medication from the perspective of organism susceptibility and lays a foundation for research on the potential mechanisms of ARs.

Genetics and Environment Distinctively Shape the Human Immune Cell Epigenome.

The epigenomic landscape of human immune cells is dynamically shaped by both genetic factors and environmental exposures. However, the relative contributions of these elements are still not fully understood. In this study, we employed single-nucleus methylation sequencing and ATAC-seq to systematically explore how pathogen and chemical exposures, along with genetic variation, influence the immune cell epigenome. We identified distinct exposure-associated differentially methylated regions (eDMRs) corresponding to each exposure, revealing how environmental factors remodel the methylome, alter immune cell states, and affect transcription factor binding. Furthermore, we observed a significant correlation between changes in DNA methylation and chromatin accessibility, underscoring the coordinated response of the epigenome. We also uncovered genotype-associated DMRs (gDMRs), demonstrating that while eDMRs are enriched in regulatory regions, gDMRs are preferentially located in gene body marks, suggesting that exposures and genetic factors exert differential regulatory control. Notably, disease-associated SNPs were frequently colocalized with meQTLs, providing new cell-type-specific insights into the genetic basis of disease. Our findings underscore the intricate interplay between genetic and environmental factors in sculpting the immune cell epigenome, offering a deeper understanding of how immune cell function is regulated in health and disease.

Effect of Periplaneta americana Residue Feed on Immunity, Antioxidant Capacity, and Transcriptome in Chickens: A Study on Sanhuang Chickens.

This study investigated the effects of Periplaneta americana residue (PAR) on the immune function, antioxidant capacity, and transcriptome of Sanhuang chickens. Six hundred 30-day-old Sanhuang chickens were divided into six groups with diets of varying PAR replacement of soybean meal from 0 to 100% in increments of 20%. Samples were taken on day 100. The results indicated that PAR did not significantly affect growth performance (p > 0.05). PAR significantly elevated the levels of IL-1β, IL-2, TNF-α, IgA, IgG, and IgM in both the serum and spleen (p < 0.05). Moreover, it markedly increased the GSH-Px, T-AOC, SOD, and CAT levels in the serum and liver (p < 0.05) and reached optimal levels of immune factors and antioxidant indicators at diet 2. Transcriptomic analysis revealed that substituting PAR for soybean meal downregulated genes associated with immune diseases and infectious disease pathways. Substituting soybean meal with PAR enhanced the resistance of Sanhuang chickens to pathogenic factors and oxidative stress, with no impact on growth performance. The optimal improvement was observed with diet 2.

The immunological landscape of primary biliary cholangitis: Mechanisms and therapeutic prospects.

Primary Biliary Cholangitis (PBC) is a chronic cholestatic liver disease characterized by the progressive destruction of intrahepatic bile ducts, leading to fibrosis, and potentially cirrhosis. PBC has been considered a prototypical autoimmune condition, given the presence of specific autoantibodies and the immune response against well-defined mitochondrial autoantigens. Further evidence supports the interaction of immunogenetic and environmental factors in the aetiology of PBC. An immunological attack on biliary epithelial cells (BECs) with secondary failure of biliary transporters, e.g. the anion exchange protein 2 (AE2), is traditionally considered the primum movens. A recent hypothesis proposes a primary failure of BECs with the downregulation of AE2 secondary to epigenetic mechanisms (miR-506 overexpression) which then triggers the immunological storm. This highlights the secretory defect as culprit and sustaining factor in the pathogenesis of PBC with UDCA helping to restore this protective mechanism by promoting bicarbonate secretion and reducing bile acid toxicity. In this review we aim to provide the most recent evidence on the immunopathogenesis of PBC. We will analyse the immune function of the biliary epithelium, assessing the immunomodulatory functions of the bile acids and the evidence of the immunological roles of the secretory pathways targeted by the current treatments.