Immuno, Volume 5, Issue 4 (December 2025) – 9 articles

Micro- and nanoplastics (MNPs) are emerging environmental immunotoxins with widespread human exposure through ingestion, inhalation, and dermal contact. Detected in the placenta, lungs, blood, bone marrow, and brain, MNPs accumulate in immune organs where they disrupt innate and adaptive cell functions. This review aims to provide a comprehensive summary of the current knowledge on how MNPs affect the immune system at the cellular and molecular levels. Experimental evidence shows that MNPs impair macrophage phagocytosis, skew dendritic cell maturation, trigger neutrophil extracellular traps, and alter T and B cell responses. Mechanistically, these effects are driven by oxidative stress, mitochondrial dysfunction, and activation of key inflammatory signaling pathways, including NF-κB, MAPK, and NLRP3 inflammasome, leading to apoptosis, pyroptosis, and chronic low-grade inflammation. Furthermore, MNP-induced disruption of epithelial barriers and gut microbiota composition undermines immune tolerance and contributes to the pathogenesis of autoimmune conditions. Preclinical models provide evidence linking MNP exposure to exacerbation of diseases such as systemic lupus erythematosus, inflammatory bowel disease, and rheumatoid arthritis. However, human epidemiological data remain limited, highlighting the urgent need for standardized exposure protocols, advanced omics technologies, and longitudinal cohort studies are urgently needed to establish causal links and inform public health strategies. Full article

Embryo implantation requires a finely tuned immune balance at the maternal–fetal interface. Interferon tau (IFN-τ), a key immunomodulator in ruminant implantation, may have therapeutic potential in human reproduction. This study investigated its effects on peripheral blood mononuclear cells (PBMCs) in vitro and the subsequent impact on endometrial immune composition following intrauterine administration of these cells. The work was conducted in two stages. First, in vitro assays were performed with PBMCs from 20 patients with recurrent implantation failure (RIF) cultured with or without IFN-τ for 24 h. Cytokines (IL-10, IL-4, TNF-α, IL-6) were measured by ELISA, and T cell subsets (Th, cytT, Th1, Th2, Th9, Tfh, Th17, Treg) were analyzed by flow cytometry. IFN-τ increased IL-4 and reduced TNF-α and IL-6, indicating a Th2 profile shift. T-cell analysis revealed fewer cytT, Th1, Th9, and Th17 cells, more Th2 cells, and improved Th/Tk, Th1/Th2, and Th17/Treg ratios after IFN-τ. A second clinical study included 55 RIF patients who received intrauterine IFN-τ-modulated PBMCs. Post-treatment endometrial biopsies revealed more helper T cells and macrophages, with higher Th/total T, Th/cytT, and Th/macrophage ratios, suggesting a tolerogenic environment. Overall, IFN-τ modulates PBMCs in vitro and promotes a favorable endometrial immune profile in vivo, highlighting its potential as an immunotherapy in assisted reproduction. Full article

The inflammatory and metabolic complexity of colitis necessitates therapies that act on multiple immune pathways. Using serum proteomic profiling, the present study evaluated the systemic immunomodulatory profile of Epilobium angustifolium lyophilized methanol-aqueous extract rich in oenothein B (EAE) in a dextran sulfate sodium (DSS)-induced mouse model of ulcerative colitis in a comparative manner to dexamethasone (DXM). DSS exposure triggered robust inflammatory activation, evidenced by elevated chemokines (CXCL9, CXCL10, CCL11), proinflammatory cytokines (IL-1α, IL-12, PAI-1, RAGE) and metabolic stress mediators (leptin, resistin, FGF-21). Treatment with EAE significantly attenuated this inflammatory profile, notably reducing Th2-skewed chemokines and eosinophil recruitment. In contrast to DXM, EAE uniquely normalized pro-thrombotic and tissue-remodeling markers, including PAI-1 and RAGE, both implicated in intestinal barrier dysfunction and chronic inflammation. Furthermore, EAE demonstrated superior modulation of inflammation-associated growth factors (IGFBP-5, HGF, Flt3L) and adipokines (leptin, resistin), indicating a broader therapeutic scope that includes metabolic dysfunctions. Collectively, our data reveal that EAE exerts a distinct immunoregulatory profile, modulating both innate and adaptive immune pathways while simultaneously addressing metabolic pathologies. These multifaceted actions underscore its promise as a phytotherapeutic candidate for the management of ulcerative colitis and other inflammatory conditions, with potential advantages over conventional steroid treatment. Full article

Background: Endometriosis, believed by many to be rooted in immunology, is a chronic disease. Upregulation of programmed cell death protein 1 (PD-1) in immune cells may compromise their defensive function, a mechanism demonstrated in the context of cancer spread. This study aims to explore the potential involvement of PD-1 in the pathophysiology and progression of endometriosis. A total of 62 patients who underwent laparoscopic surgery were analyzed, with 47 diagnosed with endometriosis and 15 serving as controls. We collected peritoneal fluid and peripheral blood samples during surgery and examined them using flow cytometry. Using a panel of monoclonal antibodies, the samples were stained and the expression of PD-1 in immune cells was evaluated. Results: We observed a statistically significant rise in the percentage of the CD56⁺ CD16⁺ NK cell subset expressing PD-1 within the peritoneal fluid of endometriosis patients compared to the control group (p = 0.021). Similarly, we found that PD-1 expression on immune cells significantly differed based on factors such as body mass index and smoking habits. Moreover, peritoneal subsets of PD-1⁺ T and NK cells showed an increase in patients presenting symptomatic endometriosis and those with more widespread disease. Conclusions: Our evaluation of the inhibitory PD-1 receptor has strengthened the potential connection between immune escape mechanisms often seen in cancer cells and those in endometriotic cells. This concept could pave the way for future research in the field of immunomodulation and endometriosis. Full article

Lung cancer is the most common cause of death due to cancer in the world, and non-small cell lung cancer (NSCLC) is the most common form of lung cancer, representing approximately 84% of all cases. Due to its frequency and mortality, the amount of research on this subject has been greatly increased and new techniques to improve health outcomes have been established. While surgery remains the gold standard of treatment, immunotherapy used alone or in conjunction with surgery shows promising results. This review aims to give an overview of current and new surgical and immunotherapy methods used for the treatment of NSCLC, as well as ways in which they can be combined and the clinical outcomes for patients with each treatment modality. Additionally, it will seek to highlight any gaps in current knowledge of treatment and propose further studies to improve the efficacy of NSCLC treatments. Full article

Neutrophils are an essential protective component of the innate immune system. However, in severe bacterial infections, neutrophils are known to mis-localise from the primary site of infection to other organs, where excessive release of cytokines, chemokines, and neutrophil extracellular traps (NETs) can induce organ damage and death. In this study, we use an animal model of bacterial infection originating in the peritoneum to show that hydrogen peroxide (H₂O₂, a potent neutrophil chemoattractant) is initially released in high concentrations both in the peritoneum and in multiple ‘off-target’ organs (lungs, liver and kidneys). The initial high H₂O₂ release inhibits neutrophil chemotaxis, but after 24 h concentrations of H₂O₂ reduce and can promote neutrophil migration to organs, where they release pro-inflammatory cytokines and chemokines along with NETs. The antimalarial compound artesunate potently inhibits neutrophil migration to off-target organs. It also abolishes cytokine, chemokine, and NET production, suggesting that artesunate may be a valuable novel therapy for preventing off-target organ inflammation associated with severe bacterial infections. Finally, the potency of H₂O₂ as a chemoattractant is shown by in vitro experiments in which, faced with competing gradients of H₂O₂ and other chemoattractants, neutrophils preferentially migrate towards H₂O₂. Full article

Immune cells like neutrophils, monocytes/macrophages, and lymphocytes play key roles in the development, progression, and resolution of deep vein thrombosis (DVT) by contributing to inflammation, coagulation, and fibrinolysis. IFN-γ, a cytokine mainly secreted by natural killer (NK) and T cells, is a critical factor in DVT pathogenesis. It links immune responses to coagulation activation by promoting endothelial activation, leukocyte recruitment, cytokine release, and coagulation imbalance. Its strong pro-inflammatory and prothrombotic effects make IFN-γ a promising target for DVT treatment beyond standard anticoagulants. Exploring ways to block IFN-γ signaling or its downstream effects could open doors to novel therapies for DVT, aiding in resolution and preventing post-thrombotic complications. This review delves into DVT pathophysiology, diagnostics, and management, emphasizing the importance of targeting immune cells and IFN-γ to advance treatment options. Full article

Cardiomyopathies affect over 3 million individuals globally, with conventional treatments exhibiting up to 60% resistance and 25% 30-day readmission rates. This review synthesizes the current evidence on the role of neuro-immune interactions in the pathogenesis of cardiomyopathy and evaluates emerging therapies targeting this axis. We systematically examined clinical trials and mechanistic and multi-omics data across cardiomyopathy phenotypes, focusing on autonomic-immune dysregulation. Sympathetic overactivation, present in approximately 85% of patients, correlates with elevated pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) and contributes significantly to therapeutic non-response. Concurrent parasympathetic withdrawal impairs cholinergic anti-inflammatory pathways, as reflected by reduced heart rate variability and baroreflex sensitivity. At the molecular level, shared mechanisms include inflammasome activation, neuroimmune synaptic signaling, and neurogenic inflammation. Emerging therapies targeting this axis are promising. Vagus nerve stimulation, as demonstrated in the INOVATE-HF trial, improves functional outcomes, whereas IL-1β antagonists reduce cardiovascular events by 15–20% in the context of inflammatory diseases. Bioelectronic interventions, such as transcutaneous vagal nerve stimulation and baroreflex activation therapy, offer noninvasive dual-modulatory strategies that address both neural and immune pathways, positioning the neuroimmune axis as a central driver of cardiomyopathy, regardless of etiology. The integration of genetic and metabolomic profiling may enable precision therapies targeting neuroimmune circuits, thereby overcoming the limitations of hemodynamic-focused care. This mechanistic framework shifts the therapeutic paradigm from symptomatic relief to targeted modulation of pathogenic pathways, with implications for millions of patients with cardiomyopathy and broader inflammatory cardiovascular disorders. Full article

Inducible forms of chronic urticaria are characterized by an early age of onset and a long duration of disease. In addition, cold and cholinergic urticaria have a risk of developing systemic, sometimes life-threatening, reactions. Determining the pathogenetic mechanisms and laboratory and clinical predictors of their development is an open question in the understanding of these diseases. This literature review demonstrates the current known facts that allow the identification of patients with cold and cholinergic urticaria in high-risk groups of anaphylaxis development and, therefore, the possibility to prevent emergency situations and to manage them in time. For cold and cholinergic urticaria, observations of Kounis syndrome–acute coronary syndrome (myocardial infarction or unstable angina) have been described. A series of trials, including the large international multicenter COLD-CE study of anaphylaxis in cold urticaria, have identified early age of urticaria onset, severe clinical symptoms, shortening of the critical temperature threshold, comorbid bronchial asthma, concomitant angioedema, and pruritus of the earlobes as warning signs. No such large-scale studies have been conducted for cholinergic urticaria. Among the few high-risk factors for systemic reactions in cholinergic urticaria described in the literature is the occurrence of angioedema. Thus, it is possible to identify some patients in the high-risk group already at the stage of initial anamnesis collection, and additional data can be collected during the examination. Laboratory biomarkers, clinical predictors, understanding the mechanisms of anaphylaxis by physical triggers or their consequences, and optimal options for pathogenetic therapy are still unresolved issues that require further research. The aim of this review is to provide a content analysis of current knowledge about chronic inducible urticarias in order to increase clinicians’ awareness and, consequently, reduce the risk of urgent conditions associated with them. Full article