Immunological Investigations最新文献

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.

Introduction: Rutin, a dietary flavonoid, exhibits anti-inflammatory, antioxidant, and immunomodulatory properties. The underlying mechanism of protection of rutin against Aflatoxin B1 (AFB1)-induced immunotoxicity is not completely elucidated. This study investigated the protective effect of rutin against Aflatoxin B1 (AFB1)-induced immunotoxicity in male Wistar rats, supported by molecular docking and dynamics simulations.

Methods: Forty male Wistar rats were grouped into five: control (corn oil), AFB₁ (0.75 mg/kg bwt), AFB₁ (1.5 mg/kg bwt), rutin (50 mg/kg bwt), and AFB₁ (1.5 mg/kg bwt) + Rutin (50 mg/kg bwt) orally for 30 days.

Results: AFB₁ exposure increased (p < 0.05) oxidative and inflammatory markers, altered hematological indices, and caused histological damage in the spleen and bone marrow. Elevated indoleamine 2,3-dioxygenase (IDO) activity, reduced CD4+ T cells, and unchanged tryptophan 2,3-dioxygenase (TDO) activity were also observed. Docking revealed strong binding affinities for AFB₁ (-9.5 kcal/mol), rutin (-9.7 kcal/mol), and AFB₁-rutin (-10.4 kcal/mol) with IDO. Rutin co-treatment restored oxidative, inflammatory, and hematological indices, mitigated histological damage, and normalized CD4+ T cells and IDO activity, as supported by computational studies.

Discussion: The activities/expression of immunosuppressive indoleamine 2, 3-dioxygenase is mostly regulated by inflammation and oxidative stress. This study provides new insights into the mechanisms underlying the modulation of immunotoxicity of AFB1 by dietary rutin.

Background: Following the bioinformatics predictions, this investigation delves into the function of FOXM1 in the phenotype of macrophages and inflammatory responses in alcoholic hepatitis (AH).

Methods: A mouse model of AH was generated using the Lieber-DeCarli method, and mouse Kupffer cells (KCs) were treated with lipopolysaccharide and ethanol. Expression of FOXM1 and S1PR1 in mouse liver tissues or KCs was determined using RT-qPCR, immunofluorescence, or western blot assays. Loss- or gain-of-function assays of FOXM1 and S1PR1 were performed, followed by histopathological staining of the liver tissues, examination of the inflammatory cytokines, and assessment of macrophage phenotype.

Results: FOXM1 exhibited heightened expression in the mouse liver tissues and KCs in AH models. Silencing FOXM1 reduced pathological injury, hepatic steatosis, alanine aminotransferase and aspartate aminotransferase levels, inflammatory cytokine production, and pro-inflammatory (M1) polarization markers of macrophages. This condition also alleviated M1 polarization of KCs in vitro. FOXM1 promoted transcription and expression of S1PR1 by binding to its promoter. The additional upregulation of S1PR1, in the presence of FOXM1, rescued M1 skewing of macrophages both in vitro and in vivo, thus aggravating inflammatory responses.

Conclusion: This study identifies that FOXM1-mediated transcriptional upregulation of S1PR1 promotes pro-inflammatory activation of macrophages and augments liver injury in AH.

Background: Antibodies have long served as fundamental tools in disease diagnosis and surveillance. Their utility as biomarkers has expanded beyond infectious diseases to encompass a wide range of health conditions.

Objectives: This review aims to explore recent advancements in antibody biomarker discovery and their applications in diagnosing and monitoring diverse health conditions. It also examines the role of antibody surveillance in public health and epidemiological studies.

Methods: A comprehensive analysis of recent literature was conducted, focusing on studies that identify and characterize disease-specific antibodies. Particular attention was given to their relevance in autoimmune diseases, infections, cancers, and neurological disorders.

Content: The review highlights disease-specific antibody biomarkers and their clinical significance. It also discusses the utility and challenges of antibody-based surveillance in assessing disease prevalence, tracking immunity trends, and supporting One Health strategies.

Conclusions: Recent advancements in antibody biomarker discovery demonstrate significant potential in improving early diagnosis, personalized treatment, and population-level health management. Antibody surveillance continues to play a pivotal role in guiding public health responses and understanding disease dynamics.

Macrophages are pivotal immune cells involved in maintaining immune homeostasis and defending against pathogens. They exhibit significant plasticity and heterogeneity, enabling polarization into pro-inflammatory M1 or anti-inflammatory M2 phenotypes in response to distinct microenvironmental cues. The process of macrophage polarization is tightly regulated by complex signaling pathways and transcriptional networks. This review explores the factors influencing macrophage polarization, the associated signaling pathways, and their roles in the pathogenesis of lung diseases, including fibrosis, cancer, and chronic inflammatory conditions. By summarizing recent advances, we aim to provide insights into the immunoregulatory functions of macrophages and their therapeutic potential. Based on our review, it is believed that targeting macrophage polarization emerges as a promising approach for developing effective treatments for lung diseases, balancing inflammation and repair while mitigating disease progression.

Objective: To investigate how a high-fat, high-sugar (HFHS) diet influences postoperative pain and inflammation, and to explore the role of NF-κB signaling and macrophage polarization.

Methods: Male Sprague Dawley rats were divided into five groups: normal diet (ND), HFHS, ND + surgery (ND + S), HFHS + surgery (HFHS + S), and HFHS + surgery + NF-κB inhibitor (HFHS + S + B). After eight weeks of diet, laparotomy was performed. Pain behavior was assessed using the Rat Grimace Scale. DRG and blood samples were collected for Western blotting, ELISA, flow cytometry, and immunofluorescence.

Results: HFHS combined with surgery significantly activated NF-κB signaling, shown by increased p65/IκBα phosphorylation and COX-2 upregulation. NF-κB inhibition reversed these effects and reduced pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, MCP-1) and pain scores. HFHS and surgery also increased M1 and decreased M2 macrophages; these changes were reversed by NF-κB blockade. Western blotting confirmed upregulation of iNOS and IL-6 and downregulation of Arg-1 and IL-10 under HFHS conditions.

Conclusion: An HFHS diet exacerbates postoperative pain and inflammation via NF-κB activation and M1 macrophage polarization. Inhibiting NF-κB may mitigate diet-induced sensitization.

Background: Single-cell RNA sequencing (scRNA-seq) has improved our ability to characterize rare cell populations. In practice, cells from different tissues or donors are simultaneously loaded onto the instrument (multiplexed) at the recommended (standard loading) or higher (superloading) numbers to save time and money. Although cost-effective, superloading can stymie computational analyses owing to high multiplet rates and sample complexity.

Methods: We compared the effects of superloading on multiplexed single-cell gene expression and T cell receptor (TCR) data generated from human thymus and blood samples from different donors.

Results: Minimal transcriptomic differences were observed between the data generated by either standard or superloading. Irrespective of the loading cell number, we found that over 50% of the T cells expressing multiple TCR chains were doublets.

Conclusion: Multiple samples can be run simultaneously without compromising data quality and subsequent analyses. However, an additional doublet removal step based on TCR configuration may improve the accuracy of T cell analysis.

Background: Previous studies have demonstrated that double-negative (DN) αβ T cells play an important role in immune responses during ischemic acute kidney injury (AKI). Here, we investigate the role of γ-chain cytokines in driving DN T cell proliferation in steady state and AKI, focusing on IL-2, IL-7, and IL-15.

Methods: We assessed DN T cell proliferation in vitro in response to IL-2, IL-7, and IL-15, with co-culture experiments using renal tubular epithelial cells (RTECs) and IL-7 blockade. In vivo, wild-type and IL-7r knockout mice were studied to evaluate the impact of IL-7 on DN T cell expansion and kidney function during AKI. Human RTECs confirmed the relevance of these findings.

Results: All three cytokines promoted DN T cell proliferation in vitro, with IL-7 inducing the most robust expansion. Co-culture experiments showed RTECs as a key IL-7 source, and blockade reduced DN T cell expansion. In vivo, IL-7 complexes administered to wild-type mice increased DN T cells and selectively expanded the PD-1+ subset. IL-7 deficiency worsened renal outcomes during AKI. Human RTECs activated peripheral human DN T cells in vitro.

Conclusion: These results establish IL-7 as pivotal for DN T cell expansion and highlight RTECs' role in DN T cell homeostasis.

Background: IL-7 is a cytokine that plays a critical role in the development and proliferation of many different immune cells. IL-7 is notably important for the proper development and activity of T cells and B cells. Additionally, the cytokine plays a role in the function of natural killer cells and dendritic cells. Because of this innate biological activity, IL-7 has gained traction as a potential immunotherapy for multiple applications.

Methods: We conducted a comprehensive literature review to explore the physiological role of IL-7 and current applications harnessing the biology of IL-7 as a therapeutic. We also investigated the ways in which IL-7 is being engineered to enhance its therapeutic potential.

Results: Notably, IL-7 has demonstrated efficacy in adoptive cell therapy models and as a vaccine adjuvant. The cytokine has also been used as a treatment for sepsis and other chronic infections. To further enhance its therapeutic efficacy, IL-7 has been engineered by fusing the cytokine to antibody fragments or other bioactive or targeting molecules. These engineered IL-7 therapeutics seek to improve the cytokine's pharmacokinetic and immunological properties and reduce off-target effects.

Conclusion: IL-7 immunotherapies largely remain at the preclinical stage, but there is growing interest in IL-7's many therapeutic applications and increasing opportunities to further engineer the molecule for future clinical translation.

Background: Systemic lupus erythematosus (SLE) is a complex autoimmune disease that affects multiple organ systems. A key element in maintaining immune tolerance and preventing autoimmunity is the role of regulatory T cells (Treg cells). Among these, HLA-DR⁺ Treg cells represent a distinct subset, and their altered expression and functionality in SLE are closely associated with the progression of the disease. This review explores the biological characteristics of HLA-DR⁺ Treg cells, their mechanisms of action in SLE, as well as their potential and the challenges they pose as therapeutic targets.

Methods and results: This review offers a comprehensive analysis of the mechanisms by which HLA-DR⁺ Treg cells regulate immune responses. It highlights their direct interactions with autoreactive T cells and antigen-presenting cells, which contribute to the suppression of autoimmunity. Additionally, the review explores the critical role of these cells in maintaining immune tolerance and their promising potential in the context of antigen-specific immunotherapy.

Discussion: The potential of HLA-DR⁺ Treg cells in the treatment of systemic lupus erythematosus (SLE) is considerable, particularly due to their capacity to generate antigen-specific Tregs. The development of Treg-based therapies, including the expansion of both polyclonal and antigen-specific Tregs, is an area of active investigation. Nonetheless, several challenges persist, such as the need to optimize protocols for Treg generation and expansion, ensure the stability of the Treg phenotype, and address potential safety concerns associated with cellular therapies.Continued research is essential to fully harness the potential of HLA-DR⁺ Treg cells in the treatment of SLE and other autoimmune diseases.