Immune-related Disorders Research Articles

Effectiveness of Bacterial Lysates as Immune-Boosting Supplements: Evaluating a Novel Approach to Immune Health

The increasing prevalence of recurrent infections and immune-related disorders has intensified the search for effective immune-modulating interventions. Bacterial lysates, derived from inactivated bacterial components, have emerged as promising immune-boosting supplements. These lysates activate both innate and adaptive immune responses by interacting with pattern recognition receptors such as Toll-like receptors (TLRs), triggering signaling pathways that enhance immune surveillance and pathogen recognition. Among the most extensively studied is OM-85, which has demonstrated efficacy in reducing the frequency and severity of respiratory tract infections (RTIs) and modulating immune pathways involved in asthma and allergic rhinitis. This review evaluates the mechanisms of action, clinical efficacy, and safety profiles of bacterial lysates, particularly focusing on their role in preventing RTIs and managing chronic inflammatory diseases. Evidence supports their potential to reduce antibiotic use and improve overall clinical outcomes in both pediatric and adult populations. Despite their general safety, certain contraindications exist, especially in patients with hypersensitivity or autoimmune conditions. Further research is required to optimize their use, particularly in immunocompromised populations and for broader applications, such as viral infections. Bacterial lysates represent a novel, cost-effective approach to enhancing immune health and reducing the global reliance on antibiotics.

Epigenetic regulation of complement C1Q gene expression.

Human C1q is a multifaceted complement protein whose functions range from activating the complement classical pathway to immunomodulation and promoting placental development and tumorigenesis. It is encoded by the C1QA, C1QB, and C1QC genes located on chromosome 1. C1q, unlike most complement components, has extrahepatic expression by a range of cells including macrophages, monocytes and immature dendritic cells. Its local synthesis under the conditions of inflammation and for the purpose of removal of altered self requires its strict transcriptional regulation. To delve into C1Q transcriptional regulation and unravel potential epigenetic influences, we conducted an in silico analysis utilizing a range of online tools and datasets. Co-expression analysis revealed tight coordination between C1QA, C1QB, and C1QC genes. Strikingly, distinct epigenetic patterns emerged across various cell types expressing or lacking these genes, with unique histone marks and DNA methylation status characterizing their regulatory landscape. Notably, the investigation extended to tumor contexts, unveiled potential epigenetic roles in malignancies. The cell type and tumor-specific histone modifications and chromatin accessibility patterns underscore the dynamic nature of epigenetic regulation of C1Q, providing crucial insights into the intricate mechanisms governing the expression of these immunologically significant genes. The findings provide a foundation for future investigations into targeted epigenetic modulation, offering insights into potential therapeutic avenues for immune-related disorders and cancer mediated via C1q.

Immunomodulation via the Endocannabinoid System: Mechanisms and Therapeutic Potentials

The endocannabinoid system (ECS) plays a crucial role in regulating immune responses, influencing both innate and adaptive immunity through its interaction with cannabinoid receptors, particularly CB2, which is predominantly expressed on immune cells. This review explores the mechanisms of ECS-mediated immunomodulation, focusing on its ability to balance pro-inflammatory and anti-inflammatory processes, thereby contributing to immune homeostasis. Endocannabinoids, such as anandamide (AEA) and 2-arachidonoylglycerol (2-AG), modulate immune cell activity, cytokine production, and migration. These actions make the ECS a promising therapeutic target for chronic inflammatory and autoimmune diseases, including rheumatoid arthritis, multiple sclerosis, and inflammatory bowel disease. Additionally, the ECS has potential applications in cancer immunotherapy by modulating the tumor microenvironment and enhancing anti-tumor immune responses. Non-psychoactive cannabinoids like cannabidiol (CBD) have emerged as attractive candidates for therapeutic use, offering anti-inflammatory benefits without the adverse psychoactive effects associated with tetrahydrocannabinol (THC). However, challenges remain in understanding the ECS’s complex interactions within the immune system and optimizing cannabinoid-based therapies for clinical use. As research progresses, the ECS may provide novel therapeutic avenues for immune regulation and disease management, contributing to improved outcomes in a variety of immune-related disorders. Keywords: Endocannabinoid system, Immunomodulation, CB2 receptors, Inflammation, Autoimmune diseases

Neudesin, a secretory protein, attenuates activation of lipopolysaccharide-stimulated macrophages by suppressing the Jak/Stat1/iNOS pathway

AimsNeudesin, a heme-binding protein previously identified for its neurotrophic activity, has been implicated in various physiological and pathological processes, including immune regulation. However, its role in inflammatory macrophages remains unclear. Herein, we investigated the function of neudesin in the regulation of inflammatory macrophages. Main methodsIn vitro experiments were performed in bone marrow-derived macrophages (BMDMs). In vivo experiments were conducted on neudesin knockout mice with a murine endotoxic shock model. Key findingsWe observed that neudesin deficiency led to elevated expression of Nos2/iNOS and increased nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated BMDMs. Further, we found that neudesin, via the ERK/MAPK signaling pathway, promotes the proteasome-mediated degradation of Stat1, resulting in suppression of NO production. Furthermore, neudesin-deficient mice exhibited higher mortality rates following LPS administration, accompanied by increased Nos2/iNOS expression and nitrated proteins in the heart, compared to that in wildtype mice. Treatment with an iNOS inhibitor drastically improved the survival rate of neudesin-deficient mice, highlighting the significance of neudesin-mediated iNOS signaling in modulating immune responses and preventing excessive inflammation. SignificanceOur findings suggest that neudesin acts as an anti-inflammatory cytokine, suppressing NO production in inflammatory macrophages, underscoring its potential as a therapeutic target for immune-related disorders.

Identification of immune-related mitochondrial metabolic disorder genes in septic shock using bioinformatics and machine learning

PurposeMitochondria are involved in septic shock and inflammatory response syndrome, which severely affects the life security of patients. It is necessary to recognize and explore the immune-mitochondrial genes in septic shock.MethodsThe GSE57065 dataset was acquired from the Gene Expression Omnibus (GEO) database and filtered by limma and the weighted correlation network analysis (WGCNA) to identify mitochondrial-related differentially expressed genes (MitoDEGs) in septic shock. The function of MitoDEGs was analyzed using the Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA), respectively. The Protein-Protein Interaction (PPI) network composed of MitoDEGs was established using Cytoscape. Support Vector Machine Recursive Feature Elimination (SVM-RFE), Random Forest (RF), and Least Absolute Shrinkage and Selection Operator (LASSO) were used to identify diagnostic MitoDEGs, which were validated using receiver operating characteristic (ROC) analysis and Quantitative Real-time Reverse Transcription Polymerase Chain Reaction (qRT-PCR). Furthermore, the infiltration of immunocytes was analyzed using CIBERSORT, and the correlation between diagnostic MitoDEGs and immunocytes was explored using Spearman.ResultsA total of 44 MitoDEGs were filtered, and functional enrichment analysis showed they were associated with mitochondrial function, and the PPI network had 457 nodes and 547 edges. Four diagnostic genes, MitoDEGs, PGS1, C6orf136, THEM4, and EPHX2, were identified by three machine learning algorithms, and qRT-PCR results obtained similar expression levels as bioinformatics analysis. Furthermore, the diagnostic model constructed by the diagnostic genes had fine diagnostic efficacy. Immunocyte infiltration analysis showed that activated immunocytes were abundant and correlated with hub genes, with neutrophils accounting for the largest proportion in septic shock.ConclusionsIn this study, we recognized four immune-mitochondrial key genes (PGS1, C6orf136, THEM4, and EPHX2) in septic shock and designed a novel gene diagnosis model that provided a new and meaningful way for the diagnosis of septic shock.

STAP2 promotes the progression of renal fibrosis via HSP27

BackgroundRenal fibrosis is a key process in the progression from acute kidney injury (AKI) to chronic kidney disease (CKD), while the intricate mechanisms of renal fibrosis remain obscure. While the signal-transducing adaptor protein 2 (STAP2) was well-studied for its notable function in inflammation and immune-related disorders, its specific implication in renal fibrosis remains unclear. This study assessed the mechanism by which STAP2 could promote the progression of renal fibrosis.MethodsThe expression level of STAP2 in fibrotic human samples, murine fibrosis models, and cellular fibrosis models was measured, respectively. Subsequently, immunoprecipitation (IP), mass spectrometry, and RNA sequencing (RNA-seq) were employed to identify HSP27 as an interacting protein and the PI3K-AKT signaling pathway. STAP2 was thereafter knocked down or overexpressed in both in vivo and in vitro models to assess the expression levels of pathway-related and fibrosis-related proteins. Finally, the important role of STAP2 in the fibrosis process in animal models induced by ischemia-reperfusion injury (IRI) and cisplatin was validated.ResultsFunctionally, in vivo assays demonstrated that the genetic knockout of STAP2 could remarkably mitigate epithelial-mesenchymal transition (EMT), diminish inflammatory cell infiltration, and reduce collagen deposition in mice with renal fibrosis. Conversely, in vitro assays employing STAP2-overexpressing cell models exacerbated the expression levels of fibrosis markers. The outcomes uncovered a potential mechanism by which STAP2 could modulate renal fibrosis through its impact on the expression level of phosphorylated HSP27, as well as modulating the PI3K/AKT signaling pathway.ConclusionsThis comprehensive investigation delineated the noticeable function of STAP2 in the advancement of renal fibrosis, and the outcomes might contribute to the development of targeted therapies concentrated on STAP2 to mitigate renal fibrosis.

Unraveling the Dual Anti-Inflammatory and Antioxidant Mechanisms of Acteoside: Computational Insights and Experimental Validation.

Acteoside (ACT) is one of the primary bioactive ingredients in Cistanche tubulosa (Schenk). Its remarkable efficacy in treating immune-related and inflammatory disorders has garnered significant interest among scientific circles. However, the anti-inflammatory and antioxidant effects of ACT and its underlying molecular mechanisms require further investigation. In this study, pharmacophore-based reverse docking and molecular dynamics simulations identified potential anti-inflammatory targets in silico. Studies conducted in vitro with lipopolysaccharide (LPS)-induced RAW264.7 cells validated the anti-inflammatory properties of ACT. Methyl thiazolyl tetrazolium (MTT) and lactate dehydrogenase (LDH) assays indicated ACT's non-toxic and growth-promoting effects on cells. ACT significantly reduced nitric oxide (NO) and reactive oxygen species (ROS) production and restored levels of antioxidant enzymes. It also decreased pro-inflammatory cytokines. Western blotting assays indicated that ACT inhibited p38, TNF-α, PI3 K/AKT, and NF-κB signaling pathways. These findings underscore ACT's ability to mitigate acute inflammation in RAW264.7 cells by modulating key signaling pathways and provide the scientific basis for enhancing the medicinal value of ACT and future drug development.

In situ cell-surface conformation of the TCR-CD3 signaling complex

The extracellular molecular organization of the individual CD3 subunits around the αβ T cell receptor (TCR) is critical for initiating T cell signaling. In this study, we incorporate photo-crosslinkers at specific sites within the TCRα, TCRβ, CD3δ, and CD3γ subunits. Through crosslinking and docking, we identify a CD3ε′-CD3γ-CD3ε-CD3δ arrangement situated around the αβTCR in situ within the cell surface environment. We demonstrate the importance of cholesterol in maintaining the stability of the complex and that the ‘in situ’ complex structure mirrors the structure from ‘detergent-purified’ complexes. In addition, mutations aimed at stabilizing extracellular TCR-CD3 interfaces lead to poor signaling, suggesting that subunit fluidity is indispensable for signaling. Finally, employing photo-crosslinking and CD3 tetramer assays, we show that the TCR-CD3 complex undergoes minimal subunit movements or reorientations upon interaction with activating antibodies and pMHC tetramers. This suggests an absence of ‘inactive-active’ conformational states in the TCR constant regions and the extracellular CD3 subunits, unlike the transmembrane regions of the complex. This study contributes a nuanced understanding of TCR signaling, which may inform the development of therapeutics for immune-related disorders.

N-acetyltransferase 10 is implicated in the pathogenesis of cycling T cell-mediated autoimmune and inflammatory disorders in mice

T cell expansion has a crucial function in both autoimmune and chronic inflammatory diseases, with cycling T cells contributing to the pathogenesis of autoimmune diseases by causing uncontrolled immune responses and tissue damage. Yet the regulatory mechanisms governing T cell expansion remain incompletely understood. Here we show that the enzyme N-acetyltransferase 10 (NAT10) regulates T cell activation and proliferation upon antigen stimulation. T cell-specific NAT10 deficiency in mice reduces the number of mature T cells in peripheral lymphoid organs. Mechanistically, NAT10 acetylates RACK1 at K185, preventing subsequent RACK1 K48-linked ubiquitination and degradation. The increased RACK1 stability alters ribosome formation and cellular metabolism, leading to enhanced supply of energy and biosynthetic precursors and, eventually, T cell proliferation. Our findings thus highlight the essential function of NAT10 in T cell self-renewal and metabolism and elucidate NAT10 mode of action for the potential development of novel therapies for immune-related disorders.

Eugenol-Loaded Lipid Nanoparticles-Derived Hydrogels Ameliorate Psoriasis-like Skin Lesions by Lowering Oxidative Stress and Modulating Inflammation.

Psoriasis is a chronic T-cell-mediated autoimmune skin disorder characterized by excessive epidermal thickening, overproliferation of keratinocyte, disruption of epidermal cell differentiation, and increased blood vessel growth in the dermal layer. Despite the common use of corticosteroids in psoriasis treatment, their limited efficacy and numerous side effects pose significant challenges. This research introduces a promising alternative approach by encapsulating eugenol (EU) in soya phosphatidylcholine (SPC) nanoparticles (EUNPs) which showed spherical shape nanoparticles with a hydrodynamic size of approximately 200 nm, polydispersity index 0.23, encapsulation efficiency of 85% having good colloidal stability indicated by ζ-potential of -27 mV. Later on, these EUNPs were formulated into a topical hydrogel system by using Carbopol 974P (EUNPGel), which exhibited superior drug loading, enhanced release kinetics for 48 h, long-term stability, and the ability to scavenge reactive oxygen species (ROS). Furthermore, EUNPs inhibited keratinocyte proliferation, induced apoptosis, and augmented the uptake of IL-6-mediated inflammation in human keratinocyte cells. Application of EUNPs-loaded gels (EUNPGel) to imiquimod-induced psoriatic lesions demonstrated effective dermal penetration, suppressed keratinocyte hyperplasia and restored epidermal growth. This led to a remarkable reduction in the Psoriasis Area and Severity Index (PASI) score from 3.75 to 0.5 within 5 days. This novel approach enhances ROS scavenging capacity, improves cellular uptake, facilitates skin penetration and retention, reduces the activity of hyperactive immune cells, and suggests potential applications for treating other immune-related disorders such as acne and atopic dermatitis.

Epigenetic programming of obesity in early life through modulation of the kynurenine pathway.

Childhood obesity is a global health concern that has its origins before birth. Although genetics plays a crucial role, increasing evidence suggests that epigenetic modifications during fetal life could also influence its incidence. In this model, during the fetal period, interactions between genetic makeup, intrauterine factors, and environmental conditions, increase the risk of childhood obesity. This is in accordance with the Developmental Origins of Health and Disease (DOHaD) hypothesis, in which specific intrauterine environments can have long-lasting effects on the immune system's essential functions during crucial stages of fetal growth, resulting in permanent changes to the immune function of the offspring. Consequently, dysfunction can consequently make the offspring more prone to inflammatory and immune-related disorders later in life. In this review, we examine how maternal inflammation could influence the risk of childhood obesity. We propose that during pregnancy, modification of the expression of critical genes in metabolic and signaling pathways, such as the kynurenine (Kyn) pathway, occurs due to increased levels of maternal inflammation. We also propose that such expression differences are mediated by epigenetic changes. Furthermore, we also hypothesize that the Kyn pathway produces metabolites that have immunoregulatory effects and may play a crucial role in regulating inflammation during pregnancy. As a result, interventions aimed at improving maternal inflammation may be able to help alleviate the risk of childhood obesity.

Current State of Therapeutics for HTLV-1

Human T cell leukaemia virus type-1 (HTLV-1) is an oncogenic retrovirus that causes lifelong infection in ~5–10 million individuals globally. It is endemic to certain First Nations populations of Northern and Central Australia, Japan, South and Central America, Africa, and the Caribbean region. HTLV-1 preferentially infects CD4+ T cells and remains in a state of reduced transcription, often being asymptomatic in the beginning of infection, with symptoms developing later in life. HTLV-1 infection is implicated in the development of adult T cell leukaemia/lymphoma (ATL) and HTLV-1-associated myelopathies (HAM), amongst other immune-related disorders. With no preventive or curative interventions, infected individuals have limited treatment options, most of which manage symptoms. The clinical burden and lack of treatment options directs the need for alternative treatment strategies for HTLV-1 infection. Recent advances have been made in the development of RNA-based antiviral therapeutics for Human Immunodeficiency Virus Type-1 (HIV-1), an analogous retrovirus that shares modes of transmission with HTLV-1. This review highlights past and ongoing efforts in the development of HTLV-1 therapeutics and vaccines, with a focus on the potential for gene therapy as a new treatment modality in light of its successes in HIV-1, as well as animal models that may help the advancement of novel antiviral and anticancer interventions.

Neutrophils exhibit flexible migration strategies and trail formation mechanisms on varying adhesive substrates

Substrate anchorage is essential for cell migration, and actin polymerization at cell front and myosin contractility at cell rear are known to govern cell forward movement. Yet their differential driving strategies for neutrophil migration on distinct adhesiveness substrates and their contributions to the migration-induced trail formation remain unclear. Here we explore the morphological changes, migration dynamics, and trail formation of neutrophils on ICAM-1 and PLL substrates, with a focus on the relationships among adhesive forces, traction forces, and out-of-plane forces. Results indicate that, on ICAM-1, neutrophil migration and trail formation rely on the coordinated interactions of Arp2/3 and myosin, along with biochemical regulation (via Syk and calpain) of adhesion and de-adhesion. This pattern leads to traction forces being concentrated at relatively fewer adhesive sites, facilitating cell forward migration. On PLL, however, neutrophils primarily depend on Arp2/3-mediated actin polymerization, resulting in a broader distribution of traction forces and weaker adhesions, which allows for higher leading-edge migrating velocities. Elevated membrane tension and out-of-plane forces generated by bleb protrusions on PLL reduce the reliance on myosin-driven contraction at the trailing edge, enabling easier tail detachment through elastic recoil. This work highlights the differential impact of substrate adhesiveness on neutrophil migration and trail formation and dynamics, providing new insights into cell migration mechanisms and potential therapeutic targets for inflammatory and immune-related disorders.

Species variations in muscle stem cell-mediated immunosuppression on T cells.

Muscle stem cells (MuSCs) are effective in treating inflammatory diseases driven by overactive innate immune responses, such as colitis and acute lung injury, due to their immunomodulatory properties. However, their potential in treating diseases driven by adaptive immune responses is still uncertain. When primed with inflammatory cytokines, MuSCs strongly suppressed T cell activation and proliferation in vitro in co-culture with activated splenocytes or peripheral blood mononuclear cells. Systemic administration of MuSCs from both mice and humans alleviated pathologies in mice with concanavalin A-induced acute liver injury, characterized by hyperactivated T lymphocytes. Importantly, MuSCs showed significant species-specific differences in their immunoregulatory functions. In mouse MuSCs (mMuSCs), deletion or inhibition of inducible nitric oxide synthase (iNOS) reduced their immunosuppressive activity, and absence of iNOS negated their therapeutic effects in liver injury. Conversely, in human MuSCs (hMuSCs), knockdown or inhibition of indoleamine 2,3-dioxygenase (IDO) eliminated their immunosuppressive effects, and loss of IDO function rendered hMuSCs ineffective in treating liver injury in mice. These results reveal significant species-specific differences in the mechanisms by which MuSCs mediate T cell immunosuppression. Mouse MuSCs rely on iNOS, while human MuSCs depend on IDO expression. This highlights the need to consider species-specific responses when evaluating MuSCs' therapeutic potential in immune-related disorders.

Rediscovering the human thymus through cutting-edge technologies.

Recent technological advances have transformed our understanding of the human thymus. Innovations such as high-resolution imaging, single-cell omics, and organoid cultures, including thymic epithelial cell (TEC) differentiation and culture, and improvements in biomaterials, have further elucidated the thymus architecture, cellular dynamics, and molecular mechanisms underlying T cell development, and have unraveled previously unrecognized levels of stromal cell heterogeneity. These advancements offer unprecedented insights into thymic biology and hold promise for the development of novel therapeutic strategies for immune-related disorders.

Adipose-derived mesenchymal stromal cells: A study on safety and efficacy in ocular inflammation.

This study explores the application of adipose-derived mesenchymal stromal cells (adMSCs) as a therapy for ocular inflammatory diseases utilizing a chronic GVHD model. Human adMSCs were administered via subconjunctival injection into mice with chronic ocular GVHD. Clinical scores and changes in T cell populations were analyzed. The study showed significant improvement in corneal integrity, including epithelial damage, opacity, thickness, and structure, after subconjunctival adMSC transplantation. Additionally, adMSC transplantation increased CD45+ and Foxp3+ Tregs while decreasing CD4+ T cells, 1IL17A+ Th17cells, and IFNγ+ Th1 cells in local cervical lymph nodes. Moreover, adMSC-conditioned media enhanced wound closure and cell migration toward the wound bed in vitro. The cells disappeared within a week suggesting that trophic factors were involved. The dual benefit of adMSCs in immune-related ocular disorders underscores their potential for clinical application. This study focuses on subconjunctival delivery, effects of adMSCs and migration post-injection, with implications for optimizing cellular therapy application. The observed dual action, combining immunomodulation and tissue repair enhancement, underscores holistic approach of adMSC therapy in regenerative medicine, making it a potent treatment for diseases involving inflammation and tissue damage in the ocular surface.

Harnessing Variability Signatures and Biological Noise May Enhance Immunotherapies' Efficacy and Act as Novel Biomarkers for Diagnosing and Monitoring Immune-Associated Disorders.

Lack of response to immunotherapies poses a significant challenge in treating immune-mediated disorders and cancers. While the mechanisms associated with poor responsiveness are not well defined and change between and among subjects, the current methods for overcoming the loss of response are insufficient. The Constrained Disorder Principle (CDP) explains biological systems based on their inherent variability, bounded by dynamic boundaries that change in response to internal and external perturbations. Inter and intra-subject variability characterize the immune system, making it difficult to provide a single therapeutic regimen to all patients and even the same patients over time. The dynamicity of the immune variability is also a significant challenge for personalizing immunotherapies. The CDP-based second-generation artificial intelligence system is an outcome-based dynamic platform that incorporates personalized variability signatures into the therapeutic regimen and may provide methods for improving the response and overcoming the loss of response to treatments. The signatures of immune variability may also offer a method for identifying new biomarkers for early diagnosis, monitoring immune-related disorders, and evaluating the response to treatments.

Postoperative pancytopenia in a patient with giant parathyroid adenoma and brown tumor: a case report

BackgroundParathyroid adenoma is the primary cause of primary hyperparathyroidism, commonly presenting with elevated parathyroid hormone (PTH) and blood calcium levels. Chronic primary hyperparathyroidism often results in bone destruction, resulting in the formation of brown tumors. The preferred clinical treatment for parathyroid adenoma is parathyroidectomy. Postoperative pancytopenia, although rare, is a critical complication that warrants further investigation into its mechanisms and management strategies.Case presentationWe present a case of a 59-year-old female patient who was admitted due to nausea and vomiting. Positron emission tomography-computed tomography (PET-CT) revealed a mass posterior to the left thyroid lobe and multiple areas of fibrocystic osteitis throughout the body. Hematological tests showed elevated serum calcium and parathyroid hormone (PTH) levels. The patient subsequently underwent parathyroidectomy, and pathological examination confirmed the presence of a parathyroid adenoma. Postoperatively, the patient developed pancytopenia and received symptomatic treatment such as correction of anemia and elevation of white blood. At the two-month follow-up, all indicators had returned to normal.ConclusionsPancytopenia is commonly seen in bone marrow diseases, infections and immune-related disorders, nutritional deficiencies, and metabolic diseases. This case confirms that pancytopenia can also occur postoperatively in patients with parathyroid adenoma. Therefore, Clinicians should be aware of the potential for postoperative pancytopenia following parathyroidectomy and the need for prompt management.

ETS Transcription Factors in Immune Cells and Immune-Related Diseases.

The development, differentiation, and function of immune cells are precisely regulated by transcription factors. The E26 transformation-specific (ETS) transcription factor family is involved in various physiological and pathological processes by regulating cell proliferation, differentiation, and apoptosis. Emerging evidence has suggested that ETS family proteins are intimately involved in the development and function of immune cells. This review summarizes the role of the ETS family in immune cells and immune-related disorders. Seven transcription factors within the ETS family, including PU.1, ETV5, ETV6, ETS1/2, ELK3, and ELF1, play essential roles in the development and function of T cells, B cells, macrophages, neutrophils, and dendritic cells. Furthermore, they are involved in the occurrence and development of immune-related diseases, including tumors, allergies, autoimmune diseases, and arteriosclerosis. This review is conducive to a comprehensive overview of the role of the ETS family in immune cells, and thus is informative for the development of novel therapeutic strategies targeting the ETS family for immune-related diseases.

Revolutionizing Cancer Treatments through Stem Cell-Derived CAR T Cells for Immunotherapy: Opening New Horizons for the Future of Oncology.

Recent advances in cellular therapies have paved the way for innovative treatments of various cancers and autoimmune disorders. Induced pluripotent stem cells (iPSCs) represent a remarkable breakthrough, offering the potential to generate patient-specific cell types for personalized as well as allogeneic therapies. This review explores the application of iPSC-derived chimeric antigen receptor (CAR) T cells, a cutting-edge approach in allogeneic cancer immunotherapies. CAR T cells are genetically engineered immune cells designed to target specific tumor antigens, and their integration with iPSC technology holds immense promise for enhancing the efficacy, safety, and scalability of cellular therapies. This review begins by elucidating the principles behind iPSC generation and differentiation into T cells, highlighting the advantage of iPSCs in providing a uniform, inexhaustible source of CAR T cells. Additionally, we discuss the genetic modification of iPSC-derived T cells to express various CARs, emphasizing the precision and flexibility this affords in designing customized therapies for a diverse range of malignancies. Notably, iPSC-derived CAR T cells demonstrate a superior proliferative capacity, persistence, and anti-tumor activity compared to their conventionally derived counterparts, offering a potential solution to challenges associated with conventional CAR T cell therapies. In conclusion, iPSC-derived CAR T cells represent a groundbreaking advancement in cellular therapies, demonstrating unparalleled potential in revolutionizing the landscape of immunotherapies. As this technology continues to evolve, it holds the promise of providing safer, more effective, and widely accessible treatment options for patients battling cancer and other immune-related disorders. This review aims to shed light on the transformative potential of iPSC-derived CAR T cells and inspire further research and development in this dynamic field.