Duval A, Meuleman MS, Grunenwald A
… +6 more, Vieira-Martins P, Dragon-Durey MA, Chauvet S, Roumenina L, Caillard S, Frémeaux-Bacchi V
Clin Exp Immunol
· 2026 Jan · PMID 41437313
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Functional approaches to properly examine individual's susceptibility to complement dysregulation are limited. We assessed ex vivo complement activation induced by sera from 38 healthy donors on resting microvascular end...Functional approaches to properly examine individual's susceptibility to complement dysregulation are limited. We assessed ex vivo complement activation induced by sera from 38 healthy donors on resting microvascular endothelial cells with or without complement dysregulation (OX-24 monoclonal antibody). Following incubation, immunofluorescence was used to quantify membrane-bound C3b/iC3b and C5b-9 with a computer-assisted method (H-score). C3a and C5a anaphylatoxins were quantified in supernatants by ELISA. Genetic sequencing of 32 donors was also performed to identify variants in alternative pathway genes. Elevated complement deposition was defined by H-scoreC3c > 50 and/or H-scoreC5b-9 > 30. Combined analysis of C3b/iC3b and C5b-9 deposition in 35 donors showed that one donor (2.8%) had an isolated increase in C3b/iC3b deposits, three (8.6%) had an isolated increase in C5b-9 deposits, and one (2.8%) had both increased C3b/iC3b and C5b-9 deposition. Genetic analysis revealed three heterozygous rare/low frequency missense variants in CFH (p.N1050Y, p.R1210C) and CFI (p.A76G) in 3/5 donors with increased complement deposition. This model revealed distinct patterns of complement activation among healthy individuals and identified a genetic basis for dysregulation in three cases. This assay offers a promising tool to study complement activity and its mechanisms in research.
Badami GD, Tamburini B, Fallo M
… +4 more, Azgomi MS, Dieli F, Caccamo N, La Manna MP
Clin Exp Immunol
· 2026 Jan · PMID 41430640
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In 2022, tuberculosis (TB) caused 1.3 million deaths worldwide, making it the second leading infectious cause of death. Diagnosing TB remains challenging because current immunological tests cannot distinguish between TB...In 2022, tuberculosis (TB) caused 1.3 million deaths worldwide, making it the second leading infectious cause of death. Diagnosing TB remains challenging because current immunological tests cannot distinguish between TB disease and TB infection (TBI). Research suggests that ratios such as monocyte-to-lymphocyte, neutrophil-to-lymphocyte, and platelet-to-lymphocyte, along with absolute counts of various blood cells, could help develop a low-cost and easy-to-use diagnostic tool to distinguish TB disease from TBI among IFN-γ release assay (IGRA)-positive subjects without relying on microbiological tests. We enrolled 112 TB-infected subjects and used blood cell count parameters and ratios to develop a TB score that can indicate TB status. We then validated the score in another cohort of IGRA-positive hospitalized patients. We developed a TB score based on 11 blood parameters to identify TB disease among IGRA-positive subjects, with 93% specificity and 71% sensitivity. This score can support physicians in making therapeutic decisions for IGRA-positive subjects, offering a practical approach to differentiate TB disease from TBI.
Jia Y, Liu D, Yuan L
… +4 more, Xia L, Shen H, Li Y, Lu J
Clin Exp Immunol
· 2026 Jan · PMID 41428639
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Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is a systemic autoimmune disease characterized by significant renal involvement, yet identifying novel biomarkers for renal complications remains a clinica...Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is a systemic autoimmune disease characterized by significant renal involvement, yet identifying novel biomarkers for renal complications remains a clinical priority. Metrnl is a recently identified immunomodulatory cytokine implicated in inflammation, but its specific role in AAV has historically been unknown. To address this, this study investigated serum Metrnl levels via ELISA in 37 patients with microscopic polyangiitis (MPA), 17 with granulomatosis with polyangiitis (GPA), and 30 healthy controls (HCs), analysing correlations with clinical parameters such as the Birmingham Vasculitis Activity Score (BVAS) and renal function indicators under false discovery rate (FDR) correction. The results demonstrated that serum Metrnl levels were significantly elevated in both MPA and GPA patients compared to HCs and exhibited a strong positive correlation with BVAS in both subgroups. Crucially, following FDR adjustment, Metrnl levels showed significant correlations with key markers of renal impairment, including creatinine, cystatin C, and estimated glomerular filtration rate (eGFR). Stratification of MPA patients based on renal function (eGFR cut-off: 60 ml/min/1.73 m²) further revealed substantially higher Metrnl levels in those with impaired renal function. Receiver operating characteristic curve analysis indicated superior diagnostic efficacy for Metrnl in identifying AAV with renal involvement [area under the curve (AUC) = 0.8150] compared to diagnosing AAV overall (AUC = 0.7214). Collectively, these findings provide the first evidence that serum Metrnl is elevated in AAV and associated with disease activity and renal dysfunction, suggesting that Metrnl warrants further investigation as a potential biomarker for renal involvement in AAV.
Nagata W, Kodama K, Nakagawa K
… +1 more, Ishizuka T
Clin Exp Immunol
· 2026 Jan · PMID 41423802
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Lysophosphatidic acid (LPA) is a crucial bioactive lipid mediator involved in various physiological processes; however, its role in macrophage polarization remains poorly understood; therefore, this study aimed to elucid...Lysophosphatidic acid (LPA) is a crucial bioactive lipid mediator involved in various physiological processes; however, its role in macrophage polarization remains poorly understood; therefore, this study aimed to elucidate the modulatory effect of LPA on macrophage polarization, particularly its ability to shift M1 macrophages towards an M2-like phenotype, using murine macrophage RAW264.7 cells to confirm the expression of LPA receptor 1 (LPAR1) through immunofluorescence staining, which revealed that treatment of resting MO macrophages with LPA decreased inflammatory cytokines (IL-6, TNF-α) and increased TGF-β, with similar effects observed in LPS-stimulated cells and reversed by the LPAR1 inhibitor AM095, and immunostaining demonstrated a notable shift from an M1- to M2-like phenotype, as evidenced by an increase in the arginase-1/CD68 ratio; furthermore, LPA significantly decreased lactate production and increased ATP production in M1 macrophages, promoting a shift towards oxidative phosphorylation and suggesting metabolic reprogramming towards an M2-like phenotype, significantly influencing macrophage polarization and promoting a shift from a pro-inflammatory M1-like phenotype to an anti-inflammatory M2-like phenotype; these results suggest that treatment with LPA may help ameliorate diseases characterized by aberrant macrophage polarization, providing insights for the development of potential therapeutic strategies for inflammatory and autoimmune diseases.
Murphy FK, Yennemadi AS, Jordan N
… +1 more, Leisching G
Clin Exp Immunol
· 2026 Jan · PMID 41420536
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Patients with systemic lupus erythematosus (SLE) exhibit significant susceptibility to severe bacterial infections, a leading cause of mortality. A key host defence mechanism is immunothrombosis, wherein activated monocy...Patients with systemic lupus erythematosus (SLE) exhibit significant susceptibility to severe bacterial infections, a leading cause of mortality. A key host defence mechanism is immunothrombosis, wherein activated monocytes rapidly upregulate tissue factor (TF) to initiate localized fibrin deposition that traps and contains pathogens. Effective immunothrombosis is therefore critical for preventing microbial dissemination. This process appears deficient in SLE, a disease defined by a systemic prothrombotic state, yet poor infection outcomes. A recently discovered molecular interaction suggests that TF directly binds to the interferon-α receptor (IFNAR1), acting as a rheostat to suppress interferon signalling. We hypothesize that in SLE, this regulatory axis is disrupted. The dominant, sustained interferon-stimulated gene (ISG) signatures in monocytes limit their capacity for TF upregulation in response to bacterial challenge, thereby impairing immunothrombosis and compromising bacterial containment. Supporting this, SLE patients with secondary antiphospholipid syndrome who have lower interferon signatures display markedly elevated TF levels and a different thrombotic profile, demonstrating the inverse relationship in a clinical subset. Furthermore, TF induction in monocytes is glycolysis-dependent, and SLE monocytes are known to have profound metabolic alterations. The chronic interferon state may thus impose a metabolic constraint that further limits the bioenergetic capacity for a robust TF response. Therefore, the confluence of interferon-driven suppression and metabolic dysfunction in SLE monocytes provides a compelling explanation for the failure of immunothrombosis, directly linking a core disease feature to infection susceptibility.
Tanimura R, Kondo Y, Sato R
… +14 more, Nishino R, Nishiyama T, Tanaka S, Shimizu M, Takahashi H, Furuyama K, Ohyama A, Kitada A, Abe S, Asashima H, Miki H, Tsuboi H, Matsumoto I, Sumida T
Clin Exp Immunol
· 2026 Jan · PMID 41414870
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Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiple organ involvement. It is known that cytokines produced from activated CD4+ T cells play a pivotal role in the development of SLE; howe...Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiple organ involvement. It is known that cytokines produced from activated CD4+ T cells play a pivotal role in the development of SLE; however, the details of pathological processes remain unclear. The purpose of this study is to elucidate the role of activated CD4+ T cells on the pathogenesis of lupus using SLE murine models induced by toll like receptor 7 agonist imiquimod (IMQ). Lupus was induced in wild-type (WT) and interferon γ (IFNγ)-deficient (IFNγ-/-) mice by topical IMQ treatment. Splenic T and B cell subsets were analyzed by flow cytometry. CD4+ T cells and B cells were isolated for co-culture to assess B cell differentiation and IgG production. Comprehensive lupus-like phenotypes were evaluated. Single-cell RNA sequencing (scRNA-seq) was performed to characterize IFNγ-associated cellular and molecular pathways. IMQ treatment increased IFNγ-producing CD4+ T cells, along with Tfh cells, Tph cells, age-associated B cells, and plasma cells in WT mice. CD4+ T cells from IMQ-treated WT mice promoted B-cell differentiation and IgG production in co-culture assays. In IFNγ-/- mice, lupus-like phenotypes were significantly attenuated, and co-cultured B cells showed reduced differentiation and IgG production. Single-cell RNA sequencing revealed that IFNγ plays a critical role in promoting B cell differentiation and autoantibody production. IFNγ derived from activated CD4+ T cells plays a critical role in driving B-cell differentiation and promoting autoantibody production in IMQ-induced lupus.
Pham TN, Coupey J, Yger F
… +3 more, Johnson A, Thariat J, Valable S
Clin Exp Immunol
· 2026 Jan · PMID 41411189
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Radiation-induced lymphopenia following brain irradiation may influence tumor response to cancer treatment. Interactions between the immune system, tumor, and radiotherapy manifest as global lymphopenia and result in cha...Radiation-induced lymphopenia following brain irradiation may influence tumor response to cancer treatment. Interactions between the immune system, tumor, and radiotherapy manifest as global lymphopenia and result in changes in B-lymphocyte and T-lymphocyte levels. We assessed the longitudinal effects of brain irradiation on B-lymphocyte and T-lymphocyte concentrations in mice with and without glioblastoma. C57BL/6 mice were either tumor-free or tumor-bearing with GL-261 glioma cells and underwent brain irradiation with 2.5 Gy fractions in an 8-fraction irradiation regimen. We employed a tree-based model to analyze the acute impact of radiation and tumor volume on B-lymphocyte and T-lymphocyte reduction (total N = 130). Next, we developed semimechanistic models to describe the recovery patterns of B-lymphocyte and T-lymphocyte postdepletion after brain irradiation in tumor-free rodents (N = 40). Finally, we applied these models to predict B- and T-lymphocyte kinetics in tumor-bearing rodents. Brain irradiation induced a 50% reduction in B-lymphocyte and T-lymphocyte. Tumor volumes exceeding 59 mm³ caused B-lymphopenia but not T-lymphopenia during brain irradiation. Radiation exposure of lymph nodes resulted in both B- and T-lymphopenia. Our models successfully described the recovery of B/T-lymphocytes following their depletion induced by irradiation. Simulations revealed that all mice experienced B-lymphopenia, with recovery occurring within 8 days. 80% of mice experienced T-lymphopenia, with an average recovery time of 3.6 days. When tumor volumes exceeded 59 mm³, mice suffered prolonged B-lymphopenia. In conclusion, this study highlights the impact of lymph node radiation exposure and tumor volume on lymphocyte reduction and the utility of modeling in predicting long-term lymphocyte levels following brain irradiation.
Clin Exp Immunol
· 2026 Jan · PMID 41410117
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In recent years, research on innate lymphoid cells (ILCs) in pericardial adipose tissue has advanced significantly. These studies have revealed their dual role in maintaining cardiovascular homeostasis and mediating dise...In recent years, research on innate lymphoid cells (ILCs) in pericardial adipose tissue has advanced significantly. These studies have revealed their dual role in maintaining cardiovascular homeostasis and mediating disease progression. Although the contribution of ILCs to cardiovascular diseases (CVDs) has garnered increasing attention, their heterogeneous nature complicates the analysis of their phenotypic and developmental characteristics. Furthermore, substantial differences in their composition, distribution, and function exist between murine and human hearts, highlighting the need for further investigation into how the high plasticity of ILCs influences disease processes. In this review, we examine the subpopulations, distribution patterns, and multifaceted roles of ILCs in the heart during CVDs, and discuss potential strategies to modulate ILC plasticity. We anticipate that, in the future, more precise immune modulation of ILCs will emerge as a promising therapeutic approach for CVDs, ultimately benefiting public health.
Clin Exp Immunol
· 2026 Jan · PMID 41403026
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Systemic autoimmune diseases have been traditionally studied with a special focus on the immune system and less attention was paid to the roles of target tissues that are being exposed to the immune assault. For many com...Systemic autoimmune diseases have been traditionally studied with a special focus on the immune system and less attention was paid to the roles of target tissues that are being exposed to the immune assault. For many common autoimmune diseases accumulating data unravel and highlight the potential role of the target tissues as orchestrators of the autoimmune responses. In this selective review, using Sjögren's disease (SjD) as a paradigm, we discuss the role of salivary gland epithelial cells (SGEC) not as innocent bystander targets of autoimmune responses, but rather as initiators and amplifiers of the inflammatory reactions. In fact, SGEC patients with Sjögren's disease are characterized by a unique phenotype which is capable of initiating and perpetuating both innate and adaptive immune responses in the glandular microenvironment. Aberrant expression and function of TLRs and IFN pathways, lymphocyte activating proteins as well as rewired cellular metabolism and antigen-presenting features, shape this distinct auto-antigenic phenotype of SGEC. These discoveries and ideas regarding the regulatory potential of the target SGEC in Sjögren's disease add a new dimension to our concept of regulatory circuits in autoimmunity.
Filbertine G, Kynoch I, Abdullah GA
… +8 more, Gill L, Grosman R, Phelan MM, McLaren Z, Deekajorndech T, Chiewchengchol D, Hirankarn N, Wright HL
Clin Exp Immunol
· 2025 Jan · PMID 41363550
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Neutrophils contribute to systemic lupus erythematosus (SLE) pathogenesis through reactive oxygen species and neutrophil extracellular trap (NET) production, and increased apoptotic debris which causes autoantibody produ...Neutrophils contribute to systemic lupus erythematosus (SLE) pathogenesis through reactive oxygen species and neutrophil extracellular trap (NET) production, and increased apoptotic debris which causes autoantibody production and immune complex formation. These processes drive inflammation and tissue damage. The aim of this study was to perform integrated transcriptomic and metabolomic analyses comparing paediatric and adult SLE neutrophils. Adult (aSLE) and paediatric (jSLE) patient and healthy adult (HA) and juvenile (HJ) control neutrophils were subjected to RNAseq and 1H-NMR metabolomics. Univariate, multivariate and multiomics enrichment analyses were conducted in R and with ingenuity pathway analysis (IPA). Transcriptomic analysis revealed distinct gene expression profiles. Adult and juvenile SLE neutrophils were enriched for genes regulating interferon (IFN)-α/β signalling, neutrophil degranulation and NET signalling pathways (IPA, adj.P-value <0.01). Gene Ontology analysis revealed enrichment in cell cycle and interferon signalling in aSLE and angiogenesis and tissue-specific development in jSLE. Metabolomic profiling identified distinct metabolic alterations in aSLE, with a greater complexity of metabolic changes in jSLE. Multivariate PLS-DA demonstrated group discrimination, particularly in aSLE (balanced accuracy 80%, sensitivity 80%). Variable importance in the projection >1 metabolites were enriched in taurine/hypotaurine and amino acid metabolism in aSLE. Integrating transcriptomic and metabolomic data strengthened IFN-α/β signalling, neutrophil degranulation and NET signalling (adj. P < 0.001). Additional metabolic pathways uniquely down-regulated in aSLE included glutamate and glutamine metabolism, nucleotide biosynthesis and tryptophan catabolism (adj.P< 0.01). In summary, neutrophils from SLE patients, especially in jSLE, displayed complex transcriptomic and metabolic profiles, with aberrant IFN responses and neutrophil activation.
Clin Exp Immunol
· 2025 Jan · PMID 41332256
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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 wi...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. Forty-six patients each with POAG and PACG and 46 healthy controls were enrolled. Flow cytometry was utilized to determine CD38 expression levels in three lymphocyte subset groups. Spearman's correlation analysis was used to investigate the correlation of CD38 expression levels with glaucoma severity. Receiver operating characteristic analysis evaluated the discriminatory power of CD38 expression for primary glaucoma. Compared with the control group, CD38 expression levels were upregulated in CD4+ T cells (P < 0.0001) and regulatory T (Treg) cells (P < 0.001) in the POAG group and in CD4+ T cells in the PACG group (P < 0.0001). Additionally, the expression levels of CD38 in CD4+ T cells (R = -0.63, P < 0.0001) and Treg cells (R = -0.44, P < 0.001) showed a negative correlation with the mean deviation in the POAG group. Areas under the receiver operating characteristic curve for distinguishing POAG using CD38 expression in CD4+ T and Treg cells were 0.745 and 0.683, respectively (both P < 0.05). To our knowledge, this is the first study to report that CD38 + CD4+ T cells and CD38+ Treg cells are associated with the onset and severity of POAG. Therefore, CD38 expression warrants further investigation as a potential immunological indicator associated with POAG.
Staudacher O, Meyer T, Akbil B
… +9 more, Mayer M, Schmoll C, Kölsch U, Unterwalder N, Slagman A, Meisel C, Goffinet C, Möckel M, von Bernuth H
Clin Exp Immunol
· 2026 Jan · PMID 41329209
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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. We hypothesized that paradoxically low expr...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. We hypothesized that paradoxically low expression of type I IFN-induced CD169/SIGLEC1 expression analyzed by flow cytometry may allow rapid screening for the presence of these autoantibodies. In a prospective cohort study, we quantified monocytic CD169/SIGLEC1 expression and neutralizing autoantibodies against type I interferons in 808 patients who presented to the emergency room with signs of acute infections during the second wave of the SARS-CoV-2 pandemic in Germany in 2021. In patients, elevated CD169/SIGLEC1 (>2400 mAb/cell) demonstrated a negative predictive value of 100% for the detection of neutralizing autoantibodies against type I interferons. Low CD169/SIGLEC1 (<2400 mAb/cell) and a CRP >50 mg/L exhibited a positive predictive value of 70% for neutralizing autoantibodies against type I interferons. We further compared the adjusted odds ratio for mortality in patients with these autoantibodies to that in patients without autoantibodies against type I interferons. Neutralizing autoantibodies against type I interferons were associated with a worse clinical outcome, independent of SARS-CoV-2 infection, implying their presence is a risk factor for a worse general outcome.
Millar L, Di Marco Barros R, Kapiris M
… +3 more, Nikolaou C, Gerlinger M, Wu Y
Clin Exp Immunol
· 2025 Jan · PMID 41325134
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Melanoma is currently the fifth most common cancer in the UK, and its incidence is rising. Although surgery is curative for many early-stage tumours, advanced disease which is inoperable has historically also been consid...Melanoma is currently the fifth most common cancer in the UK, and its incidence is rising. Although surgery is curative for many early-stage tumours, advanced disease which is inoperable has historically also been considered incurable. Recent and rapid advances in cancer immunotherapy, particularly immune checkpoint inhibitors, have now revolutionized the management of advanced melanoma with many patients likely being cured. Here, we review the immunobiology of melanoma, the growing list of standard-of-care immunotherapies and the considerations around which treatment regimen to use. We also review evidence from recent clinical trials of promising novel immunotherapies which will hopefully help patients who do not benefit from current treatments.
Moretto SL, Vitiello GAF, Banin-Hirata BK
… +3 more, Guembarovski RL, Watanabe MAE, de Oliveira KB
Clin Exp Immunol
· 2025 Jan · PMID 41317746
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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, expre...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 (BC) patients and cancer-free women and correlate them with clinical-pathological parameters. DNA extraction was performed from peripheral blood samples, and the PDCD1 genotyping was carried out by the polymerase chain reaction technique followed by enzymatic restriction. The fragments were separated by acrylamide gel electrophoresis for genotyping. In this case-control association study, it was found that carriers of the A allele of the PDCD1 rs11568821 G > A genetic polymorphism have a higher risk of developing BC (OR = 2.42; CI 95% = 1.59-3.69; P < 0.001). This polymorphism was also correlated with positivity for estrogen (τ = 0.25; P < 0.001) and progesterone receptors (τ = 0.17; P = 0.021). The haplotypic analysis also indicated that AC allele carriers have a higher risk of BC development (OR = 2.41; CI 95% = 1.58-3.69; P < 0.001), specifically luminal A subtype (OR = 3.59; CI 95% = 2.15-5.97; P < 0.001). These results indicate that the PDCD1 rs11568821 G > A polymorphism may contribute as a potential susceptibility and prognosis marker for BC, especially for ER+/PR+ subtypes, considering the importance of PD-1 inhibitor effect over antitumor response.
Yuan C, Guo RY, Yin B
… +3 more, Zhang L, Liu J, Li B
Clin Exp Immunol
· 2025 Jan · PMID 41316924
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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 antiangiogenic properties is closely...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 antiangiogenic properties is closely related to the destruction of the BBB. This study aimed to investigate whether AIMP1 contributes to BBB disruption and to explore the underlying regulatory mechanisms. An in vitro BBB model was established using a monolayer of hCMEC/D3 cells. We investigated the effects of plasma from patients with NMOSD on BBB permeability and microstructure. Additionally, the expression of AIMP1 and ZO-1 in human brain microvascular endothelial cells was examined by quantitative real-time PCR and western blot. A luciferase reporter assay was used to validate the targeting relationship between let-7f-5p and AIMP1. To further explore the role of AIMP1 in BBB permeability and its underlying molecular mechanisms, plasmid transfection was performed in hCMEC/D3 cells. Plasma from NMOSD patients significantly impaired BBB integrity, as shown by decreased endothelial cell viability, increased sodium fluorescein (Na-F) permeability, and disrupted tight junctions. AIMP1 expression was significantly upregulated (P < 0.001), while ZO-1 expression was downregulated (P < 0.001) in NMOSD plasma-treated cells. Knockdown of AIMP1 via siRNA restored ZO-1 protein levels (P = 0.011) and reduced BBB permeability (P = 0.018). Overexpression of AIMP1 led to opposite effects, further confirming its role in barrier dysfunction. A luciferase reporter assay demonstrated that miRNA let-7f-5p directly targets AIMP1. Overexpression of let-7f-5p in hCMEC/D3 cells suppressed AIMP1 expression and partially rescued ZO-1 levels, suggesting that let-7f-5p negatively regulates AIMP1-mediated BBB damage. AIMP1 contributes to BBB dysfunction in NMOSD by downregulating the tight junction protein ZO-1, and let-7f-5p may exert a protective effect by targeting AIMP1. These findings highlight a novel let-7f-5p/AIMP1/ZO-1 regulatory axis involved in BBB impairment, offering potential therapeutic implications for NMOSD.
Clin Exp Immunol
· 2025 Jan · PMID 41092132
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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...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.
Wangriatisak K, Faustini F, Filipovic M
… +4 more, Wähämaa H, Malmström V, Gunnarsson I, Oke V
Clin Exp Immunol
· 2025 Jan · PMID 41061119
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Dysregulation of interleukin (IL) 16 has been implicated in SLE, yet its cellular source and role in disease pathogenesis remain unclear. We analysed circulating IL16+ immune cells from 40 SLE patients, including 32 with...Dysregulation of interleukin (IL) 16 has been implicated in SLE, yet its cellular source and role in disease pathogenesis remain unclear. We analysed circulating IL16+ immune cells from 40 SLE patients, including 32 with active disease (SLEDAI-2K ≥ 4) using spectral flow cytometry. Plasma (pIL16) and urine IL16 (uIL16) levels were measured, and correlations with clinical variables were assessed. IL16 effects on T cell migration were studied in vitro. Active SLE patients showed broadly reduced proportions of cells expressing IL16, including CD4+T, CD8+T, B, and NK cells. This reduction was prominent in several cell subsets including Th1-like cells and plasmablasts. Further sub-analyses of lupus nephritis (LN) versus non-LN, demonstrated significantly reduced IL16 expression e.g., in Th1-like and double negative B cell subsets in LN. In parallel, SLE patients displayed increased pIL16 levels, and LN patients showed increased uIL16 which associated positively with disease activity SLEDAI-2K index and negatively with complement C4 levels and IL16+CD4+T-cell counts. In vitro, IL16 induced CXCR4 and CCR5 mediated migration of Th1-cells and attracted CD8+T cells via CXCR4, which was partially inhibited by IL16 blockade. We demonstrate reduced intracellular IL16 expression in SLE lymphocytes, with low IL16+CD4+T cell proportions in LN correlating with increased uIL16. Extracellular IL16 may drive Th1 and CD8+T cell infiltration, contributing to organ inflammation. IL16 blockade reduced T cell migration, highlighting its potential as therapeutic target.
Ni J, Liu S, Han X
… +5 more, Guo G, Zhou X, Sun H, Huang J, Xu L
Clin Exp Immunol
· 2025 Jan · PMID 41045065
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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 stud...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 aimed to elucidate the effects of post-TACE hypoxia-induced hypoxia-inducible factor-1α (HIF-1α)/WNT/β-catenin signaling on HCC progression. In this study, serum concentrations of soluble programed death ligand 1 (sPD-L1) and HIF-1α in HCC patients who underwent TACE were measured using enzyme-linked immunosorbent assay (ELISA). In vitro, WNT/β-catenin pathway activation was assessed by TOP/FOP luciferase activity, while HIF-1α-siRNA transfection was used to observe the interaction between HIF-1α and WNT/β-catenin. In vivo, mouse xenograft tumor models were used to examine the effects of programed death ligand 1 (PD-L1) on HCC progression and to verify the correlations among HIF-1α, WNT/β-catenin, and PD-L1. The mechanisms underlying hypoxia-induced PD-L1 overexpression were studied using chromatin immunoprecipitation (ChIP). We found that the median post-TACE serum sPD-L1 and HIF-1α concentrations in HCC patients were significantly higher compared to pre-TACE levels, with a significant correlation observed between sPD-L1 and HIF-1α. In vitro studies demonstrated that hypoxia promoted WNT/β-catenin activation and PD-L1 expression. HIF-1α silencing significantly inhibited WNT/β-catenin activation. In vivo, hypoxia-induced PD-L1 overexpression significantly promoted HCC progression. WNT/β-catenin activation increased PD-L1 promoter luciferase activity, and ChIP confirmed that LEF1 bound to the PD-L1 promoter in hypoxic hepatoma cells. Therefore, we concluded that the post-TACE hypoxia-induced activation of HIF-1α/WNT/β-catenin signaling could promote HCC progression by upregulating PD-L1 expression.