Neutralizing autoantibodies against type I interferons are a risk factor for multiple severe viral diseases. The timely detection of these autoantibodies remains an unmet need.

To evaluate cluster of differentiation (CD)38 expression in peripheral blood lymphocyte subsets in patients with primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG) and explore its association with glaucoma onset and severity.

Dysfunction of the blood-brain barrier (BBB) plays a pivotal role in the pathogenesis of neuromyelitis optica spectrum disorders (NMOSD). AIMP1 as a novel proinflammatory factor with anti-angiogenic properties is closely related to the destruction of the BBB. However, its role in the pathogenesis of NMOSD remains unclear.

The programmed cell death protein 1 (PD-1), expressed mainly by T lymphocytes, is an important checkpoint of the immune response and may contribute to tumorigenesis when associated with its ligands, PD-L1 or PD-L2, expressed by tumor cells. In this context, this study aimed to analyze the allelic variants rs11568821 G>A and rs41386349 C>T of the PDCD1 gene in breast cancer patients and cancer-free women and correlate them with clinical-pathological parameters.

Post-transarterial chemoembolization (TACE) hypoxia plays a crucial role in hepatocellular carcinoma (HCC) progression. However, the effects of post-TACE hypoxia on HCC progression are not fully understood yet. This study aims to elucidate the effects of post-TACE hypoxia-induced hypoxia-inducible factor-1α (HIF-1α)/WNT/β-catenin signaling on HCC progression.

Dysregulation of interleukin (IL) 16 has been implicated in SLE, yet its cellular source and role in disease pathogenesis remain unclear.

Oral keratinocytes are pivotal to the structural and immunological integrity of the oral mucosa, orchestrating mucosal defense through multifaceted immune functions. This narrative review synthesizes mechanistic insights from primary keratinocyte cultures, in vitro infection models, transcriptomic and proteomic profiling, and immunohistochemical analyses to elucidate their roles in pathogen sensing via pattern recognition receptors, antimicrobial peptide production, cytokine secretion, antigen presentation, immune modulation, and tolerance induction. The review highlights their contributions to innate and adaptive immunity, including the secretion of antimicrobial peptides such as β-defensins and the regulation of T-cell responses through major histocompatibility complex molecules. It also examines their dysregulation in chronic inflammatory conditions, such as oral lichen planus, recurrent aphthous stomatitis, and periodontitis, where altered pattern recognition receptors signaling and barrier dysfunction drive disease progression. These insights underscore the therapeutic potential of targeting keratinocyte-mediated immunity to restore mucosal homeostasis.

Children with recurrent infections present a diagnostic challenge due to the wide overlap between normal childhood infections and primary immunodeficiency diseases (PIDs). Predominantly antibody deficiencies (PADs) are the most common category of PID in this population. While many PAD cases are identified through markedly low immunoglobulins levels or reduced B cell counts, some demonstrate subtler forms such as IgG subclass deficiency (IGGSD) or specific antibody deficiency (SAD), which may present similar clinical symptoms but normal standard laboratory parameters. Diagnosing these conditions in children is particularly challenging due to the overlap with physiological immune immaturity and the high incidence of infections in early childhood. Clinicians must carefully distinguish between benign infection patterns and true immunodeficiencies to avoid missed diagnoses and unnecessary investigations. This review summarizes key findings on IGGSD and SAD, highlights their clinical relevance in paediatric practice, and evaluates current challenges in diagnosis and classification. We also discuss the overlap between these conditions and propose a structured approach to improve diagnostic consistency. Addressing these knowledge gaps is essential to optimize care for children with recurrent infections and suspected antibody deficiencies.

B-cell maturation antigen (BCMA) is a B cell surface receptor that regulates activation, proliferation and survival. BCMA can be cleaved from the cell surface, producing soluble BCMA (sBCMA), which has been studied as a disease biomarker in systemic lupus erythematosus, multiple sclerosis and multiple myeloma. Reduced sBCMA concentrations have been associated with the severity of different primary antibody deficiencies.

Epstein-Barr virus (EBV) is a ubiquitous herpesvirus with well-established oncogenic potential, contributing to various malignancies and immune-mediated diseases. Its capacity to infect and immortalize B-cells forms the basis for the generation of lymphoblastoid cell lines (LCLs), which serve as vital models in immunology, virology, and translational research. While conventional LCLs are produced by exogenous EBV infection of peripheral blood mononuclear cells, spontaneous lymphoblastoid cell lines (S-LCLs) can emerge without deliberate viral inoculation, particularly in EBV-seropositive individuals. This review highlights multiple methodologies used to establish S-LCLs, including the use of cyclosporin A, CpG DNA, checkpoint kinase inhibitors, and cytokine modulation, and presents findings from diverse clinical contexts such as autoimmune diseases, post-transplant lymphoproliferative disorders, and cancer. We discuss the biological mechanisms underpinning EBV latency and reactivation, emphasizing the viral transcriptional programs that drive B-cell transformation and persistence. Additionally, we explore how cytokines, particularly IL-10, support S-LCL survival, and how sodium butyrate and antiviral agents like acyclovir can influence EBV reactivation and replication. The review also considers the diagnostic and therapeutic relevance of LCLs, including their potential as antigen-presenting cells, vaccine platforms, and models for cellular immunotherapies such as CAR T-cells and virus-specific cytotoxic T lymphocytes. By evaluating the generation, molecular features, and immunological significance of S-LCLs, this review underscores their value in modelling EBV-driven disease and advancing novel therapeutic strategies.

Cytokine storm can result from uncontrolled proinflammatory cytokines released in SARS-CoV-2 infection that cause damage to several organs. Il-6 is one of the major mediators of cytokine storm. IFN-α2 has been reported to have anti-viral potential and the pre-infection levels of proinflammatory cytokines have been suggested to drive the fate of the disease. There is a paucity of information on how anti-viral cytokines at the onset of infection affect the disease progression. This study aims to profile IL-2, IL-6, IL-10, and IFN-α2 expression levels for 44 days post-diagnosis and their effects on recovery.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a prevalent urological disorder characterized by urinary symptoms, pelvic pain, and sexual dysfunction. The potential inhibitory effects of docosahexaenoic acid (DHA) in relation to dietary consumption on autoimmune disorders have been acknowledged. Nevertheless, the effect of consuming DHA on CP/CPPS is still uncertain. Therefore, we established an experimental autoimmune prostatitis (EAP) model, which is frequently employed in CP/CPPS research. This study aimed to investigate the effects of dietary docosahexaenoic acid (DHA) intake on EAP and to elucidate the underlying mechanisms involved. During the establishment of EAP, non-obese diabetic (NOD) mice were administered either DHA-enriched water or conventional water. The severity of EAP and the Th17 cell responses were evaluated. Furthermore, we investigated the impact of the PPARγ inhibitor GW9662 and the NF-κB activator PMA on mice with EAP that were administered DHA. The findings demonstrated that consumption of DHA reduced the severity of EAP and inhibited the production of Th17 cells. DHA was found to hinder the development of Th17 cells through the PPARγ/NF-κB/IL-17A pathway, as demonstrated by in vitro assays. The administration of GW9662 and PMA resulted in an increase in Th17 cell production, worsening the symptoms of EAP alleviated by the consumption of DHA. The present study revealed that the consumption of DHA mitigates EAP by stimulating the PPARγ/NF-κB/IL-17A pathway, thereby influencing the process of Th17 cell differentiation. The results provide a valuable understanding of the molecular pathways that contribute to the beneficial impacts of dietary variables, including DHA, on CP/CPPS.

Conventional dendritic cells (cDCs) in the gut express the vitamin A (VA)-converting enzyme retinal dehydrogenase 2 (RALDH2) and produce significant amounts of retinoic acid (RA). RA derived from gut cDCs contributes to the generation of tolerogenic responses by promoting regulatory T-cell (Treg) differentiation while inhibiting Th1 and Th17 cell differentiation. In this study, we investigated whether similar RA-mediated immunoregulatory mechanisms operate in the pancreas using an experimental autoimmune pancreatitis (AIP) model. Our previous studies have shown that activated cDCs and plasmacytoid DCs (pDCs) play crucial roles in the induction and maturation phases of experimental AIP, respectively. Pancreatic cDCs produce IFN-α/β, CXCL9, and CXCL10, which attract CD4+CXCR3+ T cells to the pancreas during the induction phase. These CD4+CXCR3+ T cells, in turn, produce CCL25, recruiting CCR9+ pDCs that secrete IFN-α/β, CXCL9, and CXCL10 during the maturation phase. Under homeostatic conditions, RALDH2 expression was higher in pancreatic cDCs than in pDCs. Pancreatic cDCs isolated from VA-deficient mice promoted CD4+ T-cell production of IFN-γ and CCL25-the latter being a chemokine implicated in AIP pathogenesis. VA deficiency increased susceptibility to experimental AIP through a process dependent on the pancreatic accumulation of CD4+CXCR3+ T cells producing CCL25. Conversely, activation of RA-mediated signaling pathways by Am80 protected mice from severe AIP by reducing the accumulation of CXCR3+ T cells producing CCL25. Collectively, these findings suggest that RA produced by cDCs protects against AIP development by inhibiting the pancreatic accumulation of CD4+CXCR3+ T cells. RA-mediated immunoregulation may serve as a potential therapeutic target for AIP.

Since its discovery in the late 18th century, the role of vaccination in preventing death and disease has expanded across many infectious diseases and cancer. Key to our understanding of vaccine immunogenicity and efficacy is knowledge of the immune system itself. Inborn errors of immunity (IEI) represent a heterogeneous group of disorders characterized by impaired function of the immune system. Patients with IEI can have variable responses to vaccinations, depending on the nature and extent of the defect. Studies performed during the recent COVID-19 pandemic have brought unique insight into vaccine immunogenicity in individuals with IEI, knowledge that can be extended to the growing number of patients with secondary immunodeficiency arising from malignancy, organ transplantation, autoimmune conditions, and their treatments. In this review, we describe vaccine immunogenicity in IEI alongside their equivalent secondary immunodeficiencies and discuss what lessons can be learned about immunization strategies more broadly.

Using flow cytometry, we assessed circulating T4sen and T8sen proportions at baseline and 3 months after initiating anti-TNF treatment in RA and SpA patients using flow cytometry. Circulating levels of cytokines were measured at baseline. These parameters were associated with demographic variables and disease activity. T4sen and T8sen were compared between RA, SpA, SjD, healthy donors, and cancer patients. T8sen, but not T4sen, accumulated more in patients with IMIDs than in patients with lung cancer and healthy donors. CMV-seropositivity was associated with the accumulation of T8sen. T8sen were associated with high IL-6 in SpA patients and high IP-10 in SjD patients. Anti-TNF did not impact the T8sen proportion of RA and SpA patients. There was a trend toward an increase in T8sen in anti-TNF nonresponders after 3 months of treatment. Senescent CD8 T cells are enriched in IMID patients, suggesting that immune aging is a shared feature of chronic inflammatory diseases. The association between T8sen and distinct inflammatory cytokines underscores the potential role of senescence in shaping immune responses in IMIDs.

We attempted to perform a comprehensive bioinformatics analysis on osteoarthritis (OA) based on the NKT-related genes and explore the clinically related critical genes. Differentially expressed genes (DEGs) and NKT-related genes from WGCNA were obtained using the dataset GSE114007, followed by intersection analysis to obtain NKT-related DEGs. Lasso regression, support vector machine, and random forest were performed to screen feature genes, followed by verification with receiver operator curves and a nomogram model. Protein-protein interaction network, gene set enrichment analysis was performed based on the four marker genes. Finally, the immune infiltration of 64 types of immune cells was analyzed between OA samples and normal samples. The significance of biomarkers was validated in clinical samples and OA mice models. A total of four NKT-related biomarker genes (CCNJ, CFI, PREX2, and SMIM13) were identified. These genes were all upregulated in OA samples. CFI exerted promising diagnostic value for OA with an AUC of 0.994 in GSE114007 training dataset and 0.98 in the validation dataset. A significantly negative correlation between CFI and NKT cells and a significantly positive correlation between CFI and conventional dendritic cells (cDC) were found. All the biomarkers were determined to be upregulated in OA patients by clinical samples. CFI knockdown significantly reduced DC infiltration and inflammation in the knee joints of OA mice models. CFI has potential value in the pathogenesis of OA and can be used as a candidate biomarker for OA diagnosis and treatment.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory disorder of the sinonasal mucosa, predominantly characterized by epithelial dysfunction and chronic heterogeneous mucosal inflammation. CRSwNP and asthma are common comorbidities with overlapping pathophysiology, epithelial impairment, and activation of downstream type 2 inflammation. Thymic stromal lymphopoietin (TSLP) is an epithelial cytokine that sits at the top of the immunological cascade and initiates and amplifies type 2-dependent and -independent inflammatory responses. Although the role of TSLP in asthma has been well described, the role of TSLP in CRSwNP has yet to be comprehensively outlined. This review examines the evidence for TSLP as a key factor in CRSwNP pathogenesis. We explore what is known about TSLP expression patterns within the sinonasal mucosa, finding that TSLP expression is increased in patients with CRSwNP compared with healthy patients, and in eosinophilic- versus non-eosinophilic CRSwNP. We discuss the impact of environmental triggers and genetic factors on TSLP expression and activity, as well as other upstream regulators of TSLP signaling. We then consider the known mechanisms and effects of TSLP signaling on the recruitment and activation of various immune and structural cell types in CRSwNP. Finally, we consider the available evidence on the therapeutic potential of targeting TSLP signaling for the treatment of CRSwNP and discuss ongoing trials of promising therapeutic candidates.

Although celiac disease (CD) current and only treatment is a life-long strict gluten-free diet (GFD), some patients suffer from persistent duodenal lesions despite years into the diet. Hence, we aimed to study the effect that the GFD elicits on the mucosal immune infiltrate from these patients.