Immunological Investigations最新文献

Background: Ankylosing spondylitis (AS) is an inflammatory autoimmune disease with complex etiology. The forkhead box O (FOXO) 1 is an important transcription factor related to proliferation, homeostasis and metabolism. Notably, the involvement of methylation and the expression of mRNA in the promoter region of the FOXO1 gene in relation to AS is still not understood.

Methods: A two-stage case-control study enrolled 60 AS patients and 60 healthy controls (HCs) for integrated demographic and clinical evaluation and DNA methylation profiling. Subsequently, FOXO1 mRNA expression was comparatively assessed in 30 AS patients and 30 hCs.

Results: The methylation levels of 2 islands and 10 sites in the promoter region of FOXO1 gene were significantly different between AS patients and healthy controls. The negative correlation between the mRNA expression and the methylation level of FOXO1 gene was revealed (r_s = -0.624, p < .001). Subgroup analyses showed that male and HLA-B27(+) having high methylation level in AS patients (p = .008; p = .036). Moreover, the level of hypermethylation was positively correlated with the clinical features like ASDAS, and negatively correlated with LYM, MON, RDW and disease duration.

Conclusion: DNA methylation and transcription of FOXO1 might be related to AS susceptibility and play an important role in the etiology of AS.

Background: Indoleamine 2,3-dioxygenase (IDO) is a heme enzyme that catalyzes the oxidative degradation of L-tryptophan (L-Trp) through the kynurenine pathway (KP), generating metabolites that regulate immune responses. These byproducts, mainly kynurenines, contribute to immunosuppression and influence immune cell differentiation, promoting regulatory T cells (Tregs) and inducing apoptosis in inflammatory cells.

Methods: We conducted a comprehensive literature review to examine the roles of IDO and KP metabolites in intracellular parasitic infections. Our analysis focused on studies involving Leishmania, Trypanosoma cruzi, Toxoplasma gondii, and Plasmodium species.

Results: IDO has a dual role in parasitic diseases: L-Trp depletion can inhibit parasite growth, but also promotes an immunosuppressive microenvironment that may facilitate pathogen persistence. This balance between host defense and immune evasion is crucial in chronic infections. We discuss how IDO activity intersects with parasite immune evasion strategies and review potential therapeutic approaches targeting the IDO-KP axis.

Conclusion: IDO plays a complex and context-dependent role in the immunopathology of intracellular parasitic infections. While it may support host defense, its immunoregulatory effects can also favor chronic infection. Therapeutically targeting the IDO pathway is a promising strategy, but requires further investigation to optimize its clinical application.

Introduction: The aim of this study was to evaluate FOXP3 expression in CD19⁺CD39⁺ and CD19⁺CD39^- B cells, and to investigate its potential regulatory role.

Methods: Peripheral B cells were obtained from 25 volunteers. FOXP3 expression at the mRNA and protein levels was analyzed in CD19⁺CD39⁺ and CD19⁺CD39^- B cells by FACS and RT-qPCR. Suppressive activity was assessed through co-cultures of PBMC with CD19⁺CD39⁺ and CD19⁺CD39^- B cells stimulated with anti-CD3/CD28, evaluating T cell proliferation and the percentage of Th1 cells.

Results: The percentage of CD19⁺CD39⁺ FOXP3⁺ B cells was higher compared to other phenotypes. There was a positive correlation between FOXP3 and CD39 in CD19⁺ B cells. FOXP3 mRNA was increased in CD19⁺CD39⁺ B cells compared to CD19⁺CD39^- B cells. CD19⁺CD39^- B cells reduced the proliferation, the percentage of Th1 cells, and expressed higher IL-10 mRNA compared to CD19⁺CD39⁺ B cells. B cell phenotypes were inversely associated with Th1 cells and CRP. CD19⁺CD39^- was associated with HOMA-β. CD19⁺CD39⁺ was inversely associated with HbA1c.

Discussion: FOXP3 is expressed on both CD19⁺CD39^- and CD19⁺CD39⁺ B lymphocytes. CD19⁺CD39^- cells showed high levels of IL-10 and low levels of FOXP3 mRNA. CD19⁺CD39^- B cells decreased the Th1 cells and were associated with β-cell function.

Objectives: This study aimed to investigate the role of T-cell imbalance in the pathogenesis of systemic lupus erythematosus (SLE), the role of Ubiquitin-binding enzyme 2N (UBC13) in the treatment of SLE.

Methods: Mice in the model group were intraperitoneally injected with normal saline. The UBC13 group was administered UBC13 recombinant protein, and the dexamethasone (DXM) group was treated with DXM for 8 weeks. Serum anti-dsDNA and ANA levels were quantified via ELISA. Histopathological changes were analyzed using H&E staining. Splenic mRNA expression of inflammatory cytokines and transcription factors was analyzed using qRT-PCR. Flow cytometry was used characterize Th1, Th2 and Treg cells populations, while western blotting was used to detect STAT3 and NF-κB signalling pathway-related proteins in thymic lysates.

Results: UBC13 administration ameliorated splenic hyperplasia and attenuated tissue damage in MRL/lpr mice, accompanied by a reduction in serum anti-dsDNA and ANA titers. Proinflammatory cytokine production, was suppressed following UBC13 intervention. Concurrently, UBC13 restored Th1/Th2 cell equilibrium and enhanced Treg cell suppressive function. Mechanistically, UBC13 inhibited NF-κB pathway activation and suppressed STAT3 phosphorylation.

Conclusion: UBC13 restores the homeostasis and function of Th1/Th2 and Treg cell through suppression of STAT3 and the NF-κB signaling pathway activation, thereby mitigating SLE-induced organ damage.

Background: Osteoblasts, derived from mesenchymal stem cells (MSCs) in the bone marrow, are responsible for bone formation. Osteoblast differentiation is orchestrated by a spectrum of biological signals, with immune-derived components serving as indispensable regulators in this network. Dysfunctional osteoblast differentiation underlies bone-related pathologies such as osteoarthritis, rheumatoid arthritis, and osteoporosis, where immune dysregulation drives inflammatory cascades that disrupt the osteoblast-osteoclast equilibrium. This bidirectional crosstalk has propelled the emergence of osteoimmunology as a pivotal discipline.

Methods: By analyzing immune cells and cytokines in the immune microenvironment, we synthesize evidence on their roles in regulating osteoblast differentiation, with focus on inflammatory bone disorders, particularly in osteoarthritis.

Results: Thus, bone growth, development, and healing are intrinsically coupled with the dynamics of the immune microenvironment, which contributes to subchondral bone sclerosis and disease progression in osteoarthritis. Therefore, targeting immune-osteoblast crosstalk offers therapeutic potential for bone pathologies.

Conclusion: This review consolidates recent advances in understanding how the immune microenvironment impacts osteoblast differentiation, aiming to provide novel insights for clinical strategies targeting bone repair and disease mitigation.

Objective: This study aimed to explore the expression and clinical relevance of Ras homolog family member A (RhoA) in T cell subsets from patients with systemic lupus erythematosus (SLE).

Methods: Peripheral blood samples were obtained from newly diagnosed SLE patients and age- and sex-matched healthy controls. T cell subpopulations were analyzed by flow cytometry to quantify RhoA levels and associated cytotoxic markers, including granzyme B (GrB) and perforin (PFFN). Publicly available single-cell RNA sequencing (scRNA-seq) data were used to validate RhoA transcriptional patterns. Diagnostic performance was evaluated using receiver operating characteristic (ROC) curve analysis.

Results: RhoA was unevenly distributed among circulating T cell populations, with the highest protein expression observed in CD8⁺ and effector memory subsets. RhoA⁺ T cells showed significantly higher GrB and PFN levels compared to their RhoA⁺ counterparts. In early-stage SLE, RhoA expression in T cells was significantly reduced compared to healthy individuals. However, a greater proportion of CD8⁺RhoA⁺ cells expressed GZMB in SLE patients. ROC analysis yielded area under the curve (AUC) values of 0.6720 for CD4⁺RhoA⁺ and 0.6635 for CD8⁺RhoA⁺ T cells.

Conclusion: RhoA⁺ T lymphocytes exhibit enhanced cytotoxic potential and may serve as early immunological markers for the identification of SLE.

Background: Within decades of breeding, the common laboratory mouse strain C57BL/6 (B6) divided into various sub-strains with B6J and B6N being most frequently used. Recent studies showed significant genetic differences affecting several physiological, biochemical, and behavioral properties. In the immunology field, however, differences between these strains have barely been characterized and the necessity to use the adequate B6 sub-strain as experimental control appears largely unrecognized.

Methods: B6J and B6N mice were tested for a potential impact of their genetic background in various immunological models including experimental antibody-mediated immune-thrombocytopenia (ITP), B-cell depletion, K/BxN arthritis model, models of acute pneumonia, and dextran sulfate sodium (DSS)-induced colitis. Additionally, gut microbiota composition was analyzed in both healthy animals and in the context of DSS colitis.

Results: B6J and B6N mice performed equally in experimental antibody-mediated immune-thrombocytopenia and B-cell depletion. However, they revealed pronounced differences in the K/BxN arthritis model as well as in models of acute pneumonia and DSS-induced colitis. Furthermore, the B6 sub-strains demonstrated remarkable differences in gut microbiota composition that were detectable already in healthy animals and became augmented in the context of DSS colitis.

Conclusion: These findings mandate that researchers must specify and match B6 sub-strain backgrounds in immunological studies to ensure reproducibility and avoid misinterpretation of genetic modifications' effects.

Background: The aim of this study was to evaluate the possible role of lipopolysaccharide-binding protein (LBP) and interleukin 6 (IL-6) in the development of digital ulcers (DUs) in Systemic sclerosis (SSc).

Methods: 60 SSc patients were enrolled and tested for serum levels of LBP and IL-6. The development of DUs was assessed in a 12-month follow-up period.

Results: Median LBP and IL-6 were 107.445 ng/mL and 10.8 pg/mL whilst 33.3% patients had LBP ≥ 11995 ng/mL and 51.7% patients had IL-6 ≥ 12.5 pg/mL. DUs history were present in 41.7% SSc patients and at follow-up 23.3% patients developed new DUs. Baseline LBP (14105 ng/mL vs 10355 ng/mL, p < .001) and IL-6 (195 pg/mL vs 9.4 ng/mL, p < .001) were higher in SSc patients with new DUs. The ROC curves showed a good diagnostic accuracy for a cut-off of LBP ≥ 11995 ng/mL [AUC = 0.804 (95% CI = 0.656-0.951), p < .001] and for a cut-off of IL-6 ≥ 12.5 pg/mL [AUC = 0.897 (95% CI = 0.783-1.000), p < .001]. Free survival from new DUs was shorter in SSc patients with increased LBP (p < .001) or IL-6 (p = .003).

Conclusions: LPB or IL-6 could play a role in digital microvascular damage of SSc patients.

Introduction: HOX transcript antisense intergenic RNA (HOTAIR) has been implicated in inflammation and vascular pathology, but its role in regulation of ADAM17 and sepsis-induced endothelial injury remains unclear.

Methods: LPS-treated human umbilical vein endothelial cells (HUVECs) modeled sepsis-induced endothelial injury, which were assessed via qRT-PCR, western blot and immunofluorescence. HOTAIR-knockout mice were treated with cecal ligation and perforation to establish sepsis model.

Results: LPS-stimulation increased expression of HOTAIR and ADAM17 and decreased miR-326 levels in HUVECs. HOTAIR-knockdown by antisense oligonucleotides (ASOs) decreased ADAM17, TNF-α production and NF-κB activities; it also alleviated endothelial inflammation, VE-cadherin integrity damage, apoptosis and barrier dysfunction, while miR-326 inhibition reversed these effects. MiR-326 inhibited TNF-α/NF-κB via targeting ADAM17. Further experiments demonstrated recombinant TNF-α reversed the inhibitory effect of HOTAIR-ASOs on LPS-triggered TNF-α/NF-κB activation and downstream endothelial injury, which were further mitigated by NF-κB or p38 MAPK inhibitors. In-vivo experiments in HOTAIR-knockout mice confirmed the role of HOTAIR/miR-326/ADAM17 in regulating NF-κB and p38 MAPK inflammation, with improved lung injury and survival following sepsis.

Discussion: The HOTAIR/miR-326/ADAM17 axis is a key regulator of inflammation, endothelial injury and barrier dysfunction during sepsis via modulation of TNF-α/NF-κB signaling, providing new insights into the mechanisms underlying endothelial injury in sepsis.

Introduction: Sepsis is caused by an uncontrolled inflammatory response and immune dysfunction, with lung injury being the most common complication and one of the leading causes of death in clinically ill patients. Interleukin 37 (IL-37) is a multifunctional cytokine that plays a vital role in various pathophysiological processes, including inflammation, infection, and immunity.

Methods: The study involved both clinical and animal experiments (establishing an animal model of sepsis-induced lung injury). Firstly, 50 patients with sepsis-induced lung injury and 50 healthy controls were included. In addition, a more in-depth study was conducted using animal models.

Results: IL-37, IL-6, PCT, and CRP levels were significantly higher in the sepsis-induced lung injury group. Correlation analysis revealed that IL-37 significantly correlated with IL-6, PCT, and CRP levels. In animal experiments, IL-37 significantly attenuated CLP-induced pulmonary edema and cellular injury while reducing the levels of inflammatory factors IL-6 and TNF-α, as well as sepsis-related inflammatory markers PCT and CRP. Moreover, IL-37 significantly downregulated the expression levels of genes and proteins of apoptosis-related molecules Caspase-3 and Bax and pathway molecules TGF-β and Smad3.

Discussion: The TGF-β/Smad3 pathway is involved in the process of IL-37 inhibiting inflammatory response and ameliorating sepsis-induced lung injury.