Immune Privilege Research Articles

Endogenous self-peptides guard immune privilege of the central nervous system.

The central nervous system (CNS), despite the presence of strategically positioned anatomical barriers designed to protect it, is not entirely isolated from the immune system1,2. In fact, it remains physically connected to and can be influenced by the peripheral immune system1. How the CNS retains such responsiveness while maintaining an immunologically unique status remains an outstanding conundrum. In searching for molecular cues that derive from the CNS and allow its direct communication with the immune system, we discovered an endogenous repertoire of CNS-derived regulatory self-peptides presented on major histocompatibility complex (MHC) II molecules at the CNS borders. During homeostasis, these regulatory self-peptides were found to be bound to MHC II molecules throughout the path of lymphatic drainage from the brain to its surrounding meninges and its draining cervical lymph nodes. With neuroinflammatory disease, however, the presentation of regulatory self-peptides diminished. Upon boosting the presentation of these regulatory self-peptides, a population of suppressor CD4+ T cells was expanded, controlling CNS autoimmunity in a CTLA-4 and TGFβ dependent manner. This unexpected discovery of CNS-derived autoimmune self-peptides may be the molecular key adapting the CNS to maintain continuous dialogue with the immune system while balancing overt autoreactivity. This sheds new light on how we conceptually think about and therapeutically target neuroinflammatory and neurodegenerative diseases.

MDA5 Is a Major Determinant of Developing Symptoms in Critically Ill COVID-19 Patients.

Apart from the skin and mucosal immune barrier, the first line of defense of the human immune system includes MDA5 (ifih1 gene) which acts as a cellular sensor protein for certain viruses including SARS-CoV-2. Upon binding with viral RNA, MDA5 activates cell-intrinsic innate immunity, humoral responses, and MAVS (mitochondrial antiviral signaling). MAVS signaling induces type I and III interferon (IFN) expressions that further induce ISGs (interferon stimulatory genes) expressions to initiate human cell-mediated immune responses and attenuate viral replication. SARS-CoV-2 counteracts by producing NSP1, NSP2, NSP3, NSP5, NSP7, NSP12, ORF3A, ORF9, N, and M protein and directs anti-MDA5 antibody production presumably to antagonize IFN signaling. Furthermore, COVID-19 resembles several diseases that carry anti-MDA5 antibodies and the current COVID-19 vaccines induced anti-MDA5 phenotypes in healthy individuals. GWAS (genome-wide association studies) identified several polymorphisms (SNPs) in the ifih1-ifn pathway genes including rs1990760 in ifih1 that are strongly associated with COVID-19, and the associated risk allele is correlated with reduced IFN production. The genetic association of SNPs in ifih1 and ifih1-ifn pathway genes reinforces the molecular findings of the critical roles of MDA5 in sensing SARS-CoV-2 and subsequently the IFN responses to inhibit viral replication and host immune evasion. Thus, MDA5 or its pathway genes could be targeted for therapeutic development of COVID-19.

Dynamics of clinical and immunological parameters in retinal pigment epithelium transplantation in the context of combined immunosuppressive therapy in the rabbit model of retinal degeneration

Progressive damage of the retinal pigment epithelium (RPE) underlies the pathogenesis of degenerative retinal diseases such as: age-related macular degeneration (AMD), Stargardt’s disease, retinitis pigmentosa, Best’s disease and others. This group of diseases led by AMD leads to irreversible loss of visual functions, blindness and disability. The possibilities of therapy of late stages of AMD are extremely limited. The most promising approach to replace the damaged retinal pigment epithelium appears to be transplantation of RPE cells derived from induced pluripotent stem cells (iPSC-RPE) into the subretinal space (SRS). Despite immune privilege in the SRS, transplantation of xenogeneic cellular material causes severe inflammation in the posterior segment of the eye and leads to graft rejection in an in vivo experiment in the absence of immunosuppression. The solution to the problem of tissue incompatibility in this case can be the use of combined immunosuppressive therapy (CIT), aimed, on the one hand, at suppression of local inflammation (in the eye) and, on the other hand, at suppression of the systemic transplantation immune response. The aim of the study: clinical and immunological analysis of the results of transplantation of IPSC-RPE suspension on the background of CIT, including single intravitreal intraoperative administration of kenalog and further systemic application of mycophenolate mofetil (MMF), in the model of RPE atrophy in rabbits. Standard and specialized ophthalmological examination was performed at early and distant terms after the intervention in order to clinically assess the posttransplantation process. To analyze the immune status, vitreous humor (VH) and blood serum (BS) of rabbits of the experimental groups were collected. The concentrations of TGF-β1, TGF-β2, and IL-2 were determined in the biomaterial using solid-phase enzyme immunoassay. According to the results of the study, subretinal transplantation of IPSC-RPE, performed against the background of combination of single intravitreal intraoperative administration of kenalog and systemic application of MMF, is a safe method, which provides preservation of the retina and other adjacent structures of the eye and allows to prevent rejection of xenogenic material during its transplantation both in a healthy eye and with pre-formed RPE atrophy, which opens perspectives for full testing of biological effects realized by IPSC-RPE.

Adeno‐associated virus vectors for gene therapy—focusing on melanoma

AbstractAdeno‐Associated Virus (AAV) vectors have been found to have great potential in the field of gene therapy due to their unique properties. These nonpathogenic vectors exhibit high tissue specificity, low immunogenicity, and sustained gene expression, enhancing their efficacy for targeted delivery. This review explores the application of AAV vectors in gene therapy. It introduces the application and development of AAV in hemophilia and Duchenne Muscular Dystrophy. The review also highlights the use of AAV vectors in melanoma gene therapy, focusing on four key areas: cancer growth intervention, targeting cancer cells, mediating immune responses, and modulating key signaling pathways. However, despite its many advantages, rAAV faces significant challenges, including host immune responses and biological barriers that limit its effectiveness. Such complexities need to be addressed; therefore, this review also discusses the application of several polymers, such as hydrogels, nanoparticles, and solid scaffolds, in the controlled delivery of AAV.

High-Throughput Discovery of Synthetic Siderophores for Trojan Horse Antibiotics.

To cause infection, bacterial pathogens must overcome host immune factors and barriers to nutrient acquisition. Reproducing these aspects of host physiology in vitro has shown great promise for antibacterial drug discovery. When used as a bacterial growth medium, human serum replicates several aspects of the host environment, including innate immunity and iron limitation. We previously reported that a high-throughput chemical screen using serum as the growth medium enabled the discovery of novel growth inhibitors overlooked by conventional screens. Here, we report that a subset of compounds from this high-throughput serum screen display an unexpected growth enhancing phenotype and are enriched for synthetic siderophores. We selected 35 compounds of diverse chemical structure and quantified their ability to enhance bacterial growth in human serum. We show that many of these compounds chelate iron, suggesting they were acting as siderophores and providing iron to the bacteria. For two different pharmacophores represented among these synthetic siderophores, conjugation to the β-lactam antibiotic ampicillin imparted iron-dependent enhancement in antibacterial activity. Conjugation of the most potent growth-enhancing synthetic siderophore with the monobactam aztreonam produced MLEB-22043, a broad-spectrum antibiotic with significantly improved activity against Klebsiella pneumoniae, Escherichia coli, Acinetobacter baumannii, and Pseudomonas aeruginosa. This synthetic siderophore-monobactam conjugate uses multiple TonB-dependent transporters for uptake into P. aeruginosa. Like aztreonam, MLEB-22043 demonstrated activity against metallo-β-lactamase expressing bacteria, and, when combined with the β-lactamase inhibitor avibactam, was active against clinical strains coexpressing the NDM-1 metallo-β-lactamase and serine β-lactamases. Our work shows that human serum is an effective bacterial growth medium for the high-throughput discovery of synthetic siderophores, enabling the development of novel Trojan Horse antibiotics.

Immunoregulation and male reproductive function: Impacts and mechanistic insights into inflammation.

This paper investigates the complex relationship between the immune system and male reproductive processes, emphasizing how chronic inflammation can adversely affect male reproductive health. The immune system plays a dual role; it protects and regulates reproductive organs and spermatogenesis while maintaining reproductive health through immune privilege in the testes and the activities of various immune cells and cytokines. However, when chronic inflammation persists or intensifies, it can disrupt this balance, leading to immune attacks on reproductive tissues and resulting in infertility.This study provides a detailed analysis of how chronic inflammation can impair sperm production, sperm quality, and the secretion of gonadal hormones both directly and indirectly. It also delves into the critical roles of testicular immune privilege, various immune cells, and cytokines in sustaining reproductive health and examines the impacts of infections, autoimmune diseases, and environmental factors on male fertility.

Nicotinamide Alleviates Synergistic Impairment of Intestinal Barrier Caused by MC-LR and NaNO2 Coexposure.

Microcystin-LR (MC-LR) and nitrites from the environment and daily life can be ingested and absorbed by humans via the digestive tract. However, their combined effects on intestinal health remain unclear. Here, the combined impact of MC-LR and sodium nitrite (NaNO2) on the intestines of mice was investigated under actual human exposure conditions. After mice were exposed to MC-LR (10, 100 μg/L) and NaNO2 (30, 300 mg/L) individual and in combination for 6 months, it was found that MC-LR and NaNO2 synergistically decreased intestinal permeability and disrupted intestinal physical, chemical, immune, and microbial barriers. In the coexposure groups, the synergistic impairment to the intestinal barrier was noted with increasing concentrations of MC-LR or NaNO2, but this adverse effect was alleviated by nicotinamide supplementation. This study underscores the potential risks of simultaneous ingestion of MC-LR and nitrite on intestinal health. The protective role of nicotinamide suggests avenues for therapeutic intervention against environmental toxin-induced intestinal impairment.

Current Scenario and Future Perspectives of Porcine Corneal Xenotransplantation.

Corneal diseases represent a significant cause of blindness worldwide, with corneal transplantation being an effective treatment to prevent vision loss. Despite substantial advances in transplantation techniques, the demand for donor corneas exceeds the available supply, particularly in developing countries. Cornea xenotransplantation has emerged as a promising strategy to address the worldwide scarcity, notably using porcine corneas. In addition to the inherent immune privilege of the cornea, the low cost of porcine breeding and the anatomical and physiological similarities between humans and pigs have made porcine corneas a viable alternative. Nonetheless, ethical concerns, specifically the risk of xenozoonotic transmission and the necessity for stringent biosafety measures, remain significant obstacles. Moreover, the success of xenotransplantation is compromised by innate and adaptive immune responses, which requires meticulous consideration and further studies. Despite these challenges, recent breakthroughs have further contributed to reducing immunogenicity while preserving the corneal architecture. Advances in genetic engineering, such as the use of CRISPR-Cas9 to eliminate critical porcine antigens, have shown promise for mitigating immune reactions. Additionally, new immunosuppressive protocols, such as have techniques like decellularization and the use of porcine-derived acellular matrices, have greatly increased graft survival in preclinical models. Future research must focus on refining immunomodulatory strategies and improving graft preparation techniques to ensure the long-term survival and safety of porcine corneal xenotransplantation in clinical trials in humans.

Complete Blood Collection-based Systemic Inflammation Biomarkers as a Severity Biomarker in Alopecia Areata: A Cross-sectional Study.

Previous studies have suggested that alopecia areata (AA) is an organ-specific disease characterized by loss of immune privilege of hair follicles. However, an increasing body of research indicates that it not only affects the skin but may also be accompanied by systemic inflammatory reactions. Therefore, searching for simple and easily available biomarkers to describe the underlying systemic inflammation in AA patients is of great clinical significance. Complete blood collection-based systemic inflammation biomarkers have been shown to be associated with the severity and prognosis of various skin and autoimmune diseases. They involve multiple cell lineages and can reveal different pathways of immune-inflammatory responses. The aim of this study was to investigate the level of complete blood collection-based systemic inflammation biomarkers in patients with AA, and to analyse their relationship with the disease severity. A total of 302 AA patients and 296 healthy controls were included in this study and the neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), systemic immune inflammation index (SII), and white blood cell/lymphocyte ratio (WLR) were calculated. The differences in these indicators between the 2 groups were compared, and the relationship between NLR, PLR, SII, WLR, and the risk of severe AA were analysed. AA patients had higher NLR, SII, and WLR compared with healthy controls (p = 0.004, 0.002, and 0.002 respectively). PLR and SII were higher in the severe AA group compared with the mild-to-moderate AA patients (p = 0.005 and 0.011 respectively). The risk of severe AA increased with the increasing of PLR, SII, NLR, and WLR (p for trend was 0.001, 0.006, 0.022, and 0.021, respectively). The levels of systemic inflammation biomark-ers in AA patients are higher than in healthy people. NLR, PLR, SII, and WLR are risk factors for severe AA, suggesting a close association between systemic inflammation and disease occurrence in AA patients.

Immune Modulation Strategies in Gene Therapy: Overcoming Immune Barriers and Enhancing Efficacy.

The immune system presents significant obstacles to gene therapy, which has limited its use in treating many illnesses. New approaches are needed to overcome these problems and improve the effectiveness of gene therapy. This study explores several techniques to immune regulation within gene therapy, a cutting-edge discipline that aims to optimise results by fine-tuning the immune response. We cover new ways to control the immune system and deliver therapeutic genes just where they are needed, including influencing immunological checkpoints, causing immunotolerance, and making smart use of immunomodulatory drugs. In addition, the study provides insight into new developments in the design of less immunogenic gene delivery vectors, which allow for the extension of transgene expression with minimal adverse immune reactions. In order to maximise the efficacy of gene-based therapies, this review analyses these novel approaches and gives a thorough overview of the present state of the art by addressing obstacles and pointing the way toward future developments in immune regulation. Not only does their integration provide new opportunities for the creation of safer and more effective gene treatments, but it also contains the key to overcome current obstacles.

Study of the driving factors of the abnormal influenza A (H3N2) epidemic in 2022 and early predictions in Xiamen, China

BackgroundInfluenza outbreaks have occurred frequently these years, especially in the summer of 2022 when the number of influenza cases in southern provinces of China increased abnormally. However, the exact evidence of the driving factors involved in the prodrome period is unclear, posing great difficulties for early and accurate prediction in practical work.MethodsIn order to avoid the serious interference of strict prevention and control measures on the analysis of influenza influencing factors during the COVID-19 epidemic period, only the impact of meteorological and air quality factors on influenza A (H3N2) in Xiamen during the non coronavirus disease 2019 (COVID-19) period (2013/01/01-202/01/24) was analyzed using the distribution lag non-linear model. Phylogenetic analysis of influenza A (H3N2) during 2013–2022 was also performed. Influenza A (H3N2) was predicted through a random forest and long short-term memory (RF-LSTM) model via actual and forecasted meteorological and influenza A (H3N2) values.ResultsTwenty nine thousand four hundred thirty five influenza cases were reported in 2022, accounting for 58.54% of the total cases during 2013–2022. A (H3N2) dominated the 2022 summer epidemic season, accounting for 95.60%. The influenza cases in the summer of 2022 accounted for 83.72% of the year and 49.02% of all influenza reported from 2013 to 2022. Among them, the A (H3N2) cases in the summer of 2022 accounted for 83.90% of all A (H3N2) reported from 2013 to 2022. Daily precipitation(20–50 mm), relative humidity (70–78%), low (≤ 3 h) and high (≥ 7 h) sunshine duration, air temperature (≤ 21 °C) and O3 concentration (≤ 30 µg/m3, > 85 µg/m3) had significant cumulative effects on influenza A (H3N2) during the non-COVID-19 period. The daily values of PRE, RHU, SSD, and TEM in the prodrome period of the abnormal influenza A (H3N2) epidemic (19–22 weeks) in the summer of 2022 were significantly different from the average values of the same period from 2013 to 2019 (P < 0.05). The minimum RHU value was 70.5%, the lowest TEM value was 16.0 °C, and there was no sunlight exposure for 9 consecutive days. The highest O3 concentration reached 164 µg/m3. The range of these factors were consistent with the risk factor range of A (H3N2). The common influenza A (H3N2) variant genotype in 2022 was 3 C.2a1b.2a.1a. It was more accurate to predict influenza A (H3N2) with meteorological forecast values than with actual values only.ConclusionThe extreme weather conditions of sustained low temperature and wet rain may have been important driving factors for the abnormal influenza A (H3N2) epidemic. A low vaccination rate, new mutated strains, and insufficient immune barriers formed by natural infections may have exacerbated this epidemic. Meteorological forecast values can aid in the early prediction of influenza outbreaks. This study can help relevant departments prepare for influenza outbreaks during extreme weather, provide a scientific basis for prevention strategies and risk warnings, better adapt to climate change, and improve public health.

Genetic Polymorphisms of Immunity Regulatory Genes and Alopecia Areata Susceptibility in Jordanian Patients

Background and Objectives: Alopecia areata (AA) is a tissue-specific immune-mediated disorder that affects hair follicles and the nail apparatus. Due to the collapse of hair follicle immune privilege in AA, hair loss ranges in severity from small, localized patches on the scalp to the loss of entire body hair. Although AA is of uncertain etiology, the disease has a common genetic basis with a number of other autoimmune diseases. Materials and Methods: To identify candidate genes that confer susceptibility to AA in the Jordanian population and further understand the disease background, we performed DNA genotyping using case–control samples of 152 patients and 150 healthy subjects. Results: While no significant result was observed in the ten single-nucleotide polymorphisms (SNPs), CLEC4D rs4304840 variants showed significant associations with AA development within our cohort (p = 0.02). The strongest associations were for the codominant and recessive forms of rs4304840 (p = 0.023 and p = 0.0061, respectively). Conclusions: These findings suggest that CLEC4D gene variants may contribute to AA pathogenesis among Jordanians. Further advanced genetic analysis and functional investigations are required to elucidate the genetic basis of the disease.

Lung-resident alveolar macrophages regulate the timing of breast cancer metastasis.

Breast disseminated cancer cells (DCCs) can remain dormant in the lungs for extended periods, but the mechanisms limiting their expansion are not well understood. Research indicates that tissue-resident alveolar macrophages suppress breast cancer metastasis in lung alveoli by inducing dormancy. Through ligand-receptor mapping and intravital imaging, it was found that alveolar macrophages express transforming growth factor (TGF)-β2. This expression, along with persistent macrophage-cancer cell interactions via the TGF-βRIII receptor, maintains cancer cells in a dormant state. Depleting alveolar macrophages or losing the TGF-β2 receptor in cancer cells triggers metastatic awakening. Aggressive breast cancer cells are either suppressed by alveolar macrophages or evade this suppression by avoiding interaction and downregulating the TGF-β2 receptor. Restoring TGF-βRIII in aggressive cells reinstates TGF-β2-mediated macrophage growth suppression. Thus, alveolar macrophages act as a metastasis immune barrier, and downregulation of TGF-β2 signaling allows cancer cells to overcome macrophage-mediated growth suppression.

Peracute Enterotoxemia in Saanen and Alpine Goat Herd

Background: Enterotoxemia" or "overeating disease" is considered a common and often fatal disease affecting the economy of small ruminant breeding systems. This study presents findings on the occurrence of a peracute form of enterotoxemia in a herd of Saanen and Alpine, including an examination of the clinical signs, post-mortem findings, and methods for diagnosis. examination of the clinical signs, post-mortem findings, and methods for diagnosis. Methods: In a herd of goats a distressing situation occurred where the goats displayed signs (Sudden death and high fever) of peracute enterotoxemia (125 kids). It is noteworthy that these goats had previously been vaccinated against enterotoxemia. The onset of the condition seemed to be linked to three instances of interruption and reconnection of concentrate feed. To obtain a definitive diagnosis, the findings from postmortem examinations and ELISA were utilized. Results: In total, 60 Alpine and 65 Saanen succumbed to this peracute form. These losses occurred over three days but were successfully stopped by re-vaccination after two days. Clinical signs, postmortem observations, bacterial analysis, and ELISA results all provided confirmation of enterotoxemia. Notable findings included high fever (90%), duodenum hyperemia (89%), pulmonary edema (82%), convulsions (43%), and hemorrhage in the pericardium and endocardium (58%). Conclusion: Frequent and consecutive changes in goats' diet or discontinuation of concentrate supply by breeders can disrupt the vaccine-induced immune barrier, increasing the likelihood of enterotoxemia, and leading to casualties and economic losses. Consistent and stable nutrition practices are essential for maintaining vaccination efficacy and preventing enterotoxemia in goats, particularly kids.

A novel arabinogalactan extracted from Epiphyllum oxypetalum (DC.) Haw improves the immunity and gut microbiota in cyclophosphamide‐induced immunosuppressed mice

AbstractA novel type I arabinogalactan (AG‐I) polysaccharide (EPS) from Epiphyllum oxypetalum (DC.) Haw's flowers is hypothesized to possess immunomodulatory activity. This study investigated EPS's effects on immune functions and its potential mechanism for enhancing intestinal health in immunosuppressed mice. The results showed that supplementing EPS significantly alleviated immune organ damage, increased the thymus index (p &lt; 0.01), and regulated the key immune factors, including the tumor necrosis factor‐alpha (TNF‐α), immunoglobulin A (IgA), and complement 3 (C3) in the liver (p &lt; 0.05). EPS promoted the expression of intestinal immune barrier and chemical barrier proteins such as interferon‐γ (IFN‐γ) and mucin 2 (MUC2) (p &lt; 0.05), effectively repairing intestinal damage. EPS improved the diversity and structure of intestinal microbiota in immunosuppressed mice (p &lt; 0.05) and significantly altered the abundance of intestinal immune‐related microbial taxa, including Lactobacillaceae and Lactobacillus (p &lt; 0.01). Furthermore, EPS supplementation altered intestinal lactic acid metabolism, significantly increasing lactic acid levels by up to 3.4‐fold (p &lt; 0.01), and enhanced the expression of Gpr81, Wnt3a, and β‐catenin proteins at the bottom of the colonic crypts, which may repair the intestinal physical barrier. Overall, EPS represents a novel AG‐I immunomodulatory dietary polysaccharide that enhances immunity and improves gut health.

Rebalancing immune homeostasis in combating disease: the impact of medicine food homology plants and gut microbiome

BackgroundGut microbiota plays an important role in multiple human physiological processes and an imbalance in it, including the species, abundance, and metabolites can lead to diseases. These enteric microorganisms modulate immune homeostasis by presenting a myriad of antigenic determinants and microbial metabolites. Medicinal and food homologous (MFH) plants, edible herbal materials for both medicine and food, are important parts of Traditional Chinese Medicine (TCM). MFH plants have drawn much attention due to their strong biological activity and low toxicity. However, the interplay of MFH and gut microbiota in rebalancing the immune homeostasis in combating diseases needs systematic illumination. PurposeThe review discusses the interaction between MFH and gut microbiota, including the effect of MFH on the major group of gut microbiota and the metabolic effect of gut microbiota on MFH. Moreover, how gut microbiota influences the immune system in terms of innate and adaptive immunity is addressed. Finally, the immunoregulatory mechanisms of MFH in regulation of host pathophysiology via gut microbiota are summarized. MethodsLiterature was searched, analyzed, and collected using databases, including PubMed, Web of Science, and Google Scholar using relevant keywords. The obtained articles were screened and summarized by the research content of MFH and gut microbiota in immune regulation. ResultsThe review demonstrates the interaction between MFH and gut microbiota in disease prevention and treatment. Not only do the intestinal microorganisms and intestinal mucosa constitute an important immune barrier of the human body, but also lymphoid tissue and diffused immune cells within the mucosa participate in the response of innate immunity and adaptive immunity. MFH modulates immune regulation by affecting intestinal flora, helps maintain the balance of the immune system and interfere with the occurrence and development of a broad category of diseases. ConclusionBeing absorbed from the gastrointestinal tract, MFH can have profound effects on gut microbiota. In turn, the gut microbiota also actively participate in the bioconversion of complex constituents from MFH, which could further influence their physiological and pharmacological properties. The review deepens the understanding of the relationship among MFH, gut microbiota, immune system, and human diseases and further promotes the progression of additional relevant research.

Mesenchymal Stem Cells Derived from Human Urine-Derived iPSCs Exhibit Low Immunogenicity and Reduced Immunomodulatory Profile.

Human-induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSCs) represent a promising and renewable cell source for therapeutic applications. A systematic evaluation of the immunological properties and engraftment potential of iMSCs generated from urine-derived iPSCs is lacking, which has impeded their broader application. In this study, we differentiated urine-derived iPSCs into iMSCs and assessed their fundamental MSC characteristics, immunogenicity, immunomodulatory capacity and in vivo engraftment. Compared to umbilical cord-derived MSCs (UCMSCs), iMSCs demonstrated an enhanced proliferative capacity, a higher level of regenerative gene expression, and lower immunogenicity, strengthening resistance to apoptosis induced by allogeneic peripheral blood mononuclear cells (PBMCs) and the NK-92 cell line. In addition, iMSCs exhibited a diminished ability to inhibit T cell proliferation and activation compared with UCMSCs. Transcriptomic analyses further revealed the decreased expression of immune regulatory factors in iMSCs. After transfusion into mouse models, iMSCs engrafted in the lungs, liver, and spleen and exhibited the ability to migrate to tumor tissues. Our results indicated that iMSCs generated from urine-derived iPSCs have a significant replicative capacity, low immunogenicity and unique immunomodulatory properties, and hence offer obvious advantages in immune privilege and allogenic therapeutic application prospects.

Unraveling the Role of the Skin Microbiome in Immunodermatological Diseases: Implications for Therapeutic Interventions

The skin microbiome, comprising diverse microbial communities, plays a pivotal role in maintaining cutaneous homeostasis and modulating immune responses in immunodermatological diseases. This review provides an overview of recent research investigating the interplay between the skin microbiome and autoimmune, allergic, and inflammatory skin conditions, such as psoriasis, eczema, and acne vulgaris. This literature review was conducted using PubMed, searching the keywords "skin microbiome and immunodermatological diseases," "therapeutic interventions for skin microbiota," "skin disease and microbiome-host interaction," “immune response in dermatology,” “cutaneous microbiome,” "skin microbiome and allergies," "inflammatory skin conditions and microbiome," and “immune-mediated skin diseases.” A total of 53 articles were included in this review. Current evidence suggests that alterations in the skin microbiome composition, termed dysbiosis, may contribute to disease pathogenesis and exacerbate inflammation in immunodermatological disorders. Furthermore, microbial-derived metabolites and immune-modulating factors produced by commensal bacteria can influence local immune responses and skin barrier function. Future research directions include evaluating the mechanisms by which the skin microbiome interacts with the host immune system, identifying microbial biomarkers for disease diagnosis and prognosis, and exploring microbiome-targeted therapeutic interventions, such as probiotics, microbial transplantation, and microbial metabolite supplementation. By leveraging insights from microbiome research, personalized approaches to managing immunodermatological diseases may offer novel therapeutic avenues for restoring skin immune homeostasis and improving patient outcomes.

Establishment of tumor microenvironment following bisphenol A exposure in the testis

Although detrimental roles of bisphenol A (BPA) in xenoestrogen target organs, testis and epididymis, and male fertility are well-documented, disruption of the immune privilege system in the male reproductive tract following BPA exposure remains poorly understood. Therefore, this study aimed to explore the precise mechanisms of BPA in interfering immune privilege in the testis on RNA sequencing results. CD-1 male mice were daily treated no-observed-adverse-effect (NOAEL, 5 mg BPA/kg BW) and lowest-observed-adverse-effects (LOAEL, 50 mg BPA/kg BW) of BPA by oral gavage for 6 weeks. Following the LOAEL exposure, the expression of immune response-associated transcripts was upregulated in the testis. Moreover, BPA switch the testicular microenvironment to tumor friendly through the recruitment of tumor associated macrophages (TAMs), which can produce both anti- and pro-inflammatory cytokines, such as TNF-α, TLR2, IL-10, and CXCL9. Number of testicular blood vessels were approximately 2-times increased by upregulation of matrix metallopeptidase 2 in TAMs and upregulation of AR expression in the nucleus of Leydig cells. Moreover, we found that the tumor-supportive environment can also be generated even though NOAEL BPA concentration due to the individual’s variability in cancer susceptibility.

Advances in omics data for eosinophilic esophagitis: moving towards multi-omics analyses.

Eosinophilic esophagitis (EoE) is a chronic, allergic inflammatory disease of the esophagus characterized by eosinophil accumulation and has a growing global prevalence. EoE significantly impairs quality of life and poses a substantial burden on healthcare resources. Currently, only two FDA-approved medications exist for EoE, highlighting the need for broader research into its management and prevention. Recent advancements in omics technologies, such as genomics, epigenetics, transcriptomics, proteomics, and others, offer new insights into the genetic and immunologic mechanisms underlying EoE. Genomic studies have identified genetic loci and mutations associated with EoE, revealing predispositions that vary by ancestry and indicating EoE's complex genetic basis. Epigenetic studies have uncovered changes in DNA methylation and chromatin structure that affect gene expression, influencing EoE pathology. Transcriptomic analyses have revealed a distinct gene expression profile in EoE, dominated by genes involved in activated type 2 immunity and epithelial barrier function. Proteomic approaches have furthered the understanding of EoE mechanisms, identifying potential new biomarkers and therapeutic targets. However, challenges in integrating diverse omics data persist, largely due to their complexity and the need for advanced computational methods. Machine learning is emerging as a valuable tool for analyzing extensive and intricate datasets, potentially revealing new aspects of EoE pathogenesis. The integration of multi-omics data through sophisticated computational approaches promises significant advancements in our understanding of EoE, improving diagnostics, and enhancing treatment effectiveness. This review synthesizes current omics research and explores future directions for comprehensively understanding the disease mechanisms in EoE.