Frontiers in Immunology最新文献

Background: Cognitive and affective disturbances are frequent extra-thyroidal manifestations of Hashimoto's thyroiditis (HT), even in euthyroid patients, with severe cases progressing to Hashimoto's encephalopathy. The mechanisms underlying these CNS complications are still unclear; however, neuroinflammation-driven by CD4⁺ T cells and Hmgb1-mediated glial activation-is increasingly implicated. To elucidate this link, we explore in an experimental autoimmune thyroiditis (EAT) model whether Hmgb1 amplifies immune pathways to exacerbate cognitive and emotional impairments.

Methods: In C57BL/6 mice, EAT was induced by multiple injections of pTg. Histopathological analysis and ELISA confirmed the induction of thyroiditis. Exploratory behavior was assessed in an open field test, and associative memory was evaluated using the novel object recognition task, Y-maze, and Morris water maze. PCR was performed to detect inflammatory markers indicative of neuroinflammation. Furthermore, Western blotting was used to assess Hmgb1 release, and immunofluorescence (IF) was employed to examine the cytoplasmic translocation of Hmgb1 in brain sections, as well as the morphology and activation markers of microglia and astrocytes.

Results: Mice with EAT, despite preserved systemic thyroid hormone levels, displayed significant deficits in both spatial and recognition memory. Histological and immunofluorescence analyses revealed pronounced activation of microglia in the cortex and hippocampus, accompanied by an increased number of A1-like astrocytes and disrupted polarization of AQP4. Infiltrating CD4⁺ T cells were detected in these regions and were found to secrete IL-17A. Neuroinflammatory changes were associated with elevated Hmgb1 expression and increased numbers of CD68⁺ microglia, as confirmed by co-localization analyses. Pharmacological inhibition of Hmgb1 markedly reduced microglial activation and alleviated cognitive impairments.

Conclusions: Our results identify Hmgb1 as a key factor that translates peripheral thyroid autoimmunity into central neuroinflammation. It functions as a driving force behind pathogenic glial and Th17/IL-17A responses, which propagate neurotoxicity and lead to cognitive-affective dysfunction. Targeting Hmgb1 may thus offer a viable therapeutic approach to prevent or treat neurological symptoms associated with HT.

[This corrects the article DOI: 10.3389/fimmu.2025.1729080.].

γδ T cells gain increasing attention as carriers for tumor-targeting constructs in therapeutic contexts. However, the failure to fully account for the diversity within the subset has impeded its clinical use so far. We investigated the heterogeneity of the Vγ9Vδ2 T-cell compartment by profiling the function and gene expression of single-cell clones expanded in vitro using the rapid expansion protocol (REP), which involves repeated stimulation with interleukin (IL)-2 and IL-15. Generally known to enhance the type 1 effector program in the γδ T cells, these culture conditions polarized only a proportion of the adult peripheral blood-derived clones toward "classic" type 1 effectors marked by high interferon gamma (IFN-γ) release (HIR). Unexpectedly, a substantial fraction of the clones exhibited a low-IFN-γ-releasing (LIR) profile and instead activated a type 2-like effector program, marked by IL-4 and IL-5 secretion and expression of the transcription factor GATA3. In line with this functional dichotomy, we observed coordinated transcriptional programs linking effector function to genes associated with T-cell activation, proliferation, and cytokine production. HIR clones exhibited a more activated transcriptional profile in culture compared with LIR clones. Importantly, projection of HIR and LIR gene signatures onto ex vivo single-cell transcriptomic data demonstrated that these effector states are already present in vivo as part of a continuous activation landscape within nonexpanded Vγ9Vδ2 T cells, with LIR-like states predominating in cord blood and remaining prevalent in adult peripheral blood. These findings indicate that the functional divergence observed after in vitro expansion reflects stabilization and amplification of preexisting activation states rather than culture-induced polarization. Analysis of the Vγ9Vδ2 T-cell receptor repertoire further suggested that intrinsic signaling features may modulate, but do not dictate, effector differentiation within this activation continuum. In summary, our data indicate that effector differentiation of Vγ9Vδ2 T cells is dominated by a preexisting LIR-like activation state, a finding with major implications for current γδ T-cell-based cancer immunotherapy strategies that rely on in vivo stimulation or ex vivo engineering.

Chronic stress, a sustained psychophysiological state, promotes tumor progression primarily by disrupting anti-tumor immunity. Through persistent activation of the HPA axis and sympathetic nervous system, stress hormones such as glucocorticoids and catecholamines reshape the tumor microenvironment and systemically impair immune surveillance. This leads to suppressed activity of cytotoxic lymphocytes, expansion of immunosuppressive cells, and ultimately, enhanced immune evasion and metastasis. Furthermore, these pathways undermine the efficacy of conventional and emerging therapies by fostering multidrug resistance. This review highlights these mechanisms and discusses the promise of targeting stress signaling, through both pharmacological and behavioral interventions, as a strategy to improve cancer outcomes. To address the current lack of clinical guidelines for counteracting the cancer progression mediated by chronic stress, this review propose a tiered screening and intervention model based on easily accessible biostress biomarkers. This hypothesis aims to bridge the gap between basic mechanism research and clinical application, providing a theoretical foundation directional guidance for future research.

The core mechanism of acupuncture therapy lies in converting local mechanical stimulation into systemic physiological regulatory effects. Building on this concept, this review highlights the central role of macrophages in this mechanotransduction event, mainly occurring in the acupoint(s). During acupuncture, the practitioner's manipulation techniques, such as lifting-thrusting and twisting, cause significant mechanical stress at an acupoint through the entanglement and traction of collagen fibers through the acupuncture needle. This physical signal is transmitted through the extracellular matrix (ECM) and delivered to the mechanosensitive cells, such as fibroblasts and macrophages. Concurrently, while fibroblasts receive the mechanical stimuli, they also release alarmin proteins, such as interleukin-33 (IL-33), to further regulate macrophages' activities. As a key mechanical sensing and effect unit, macrophages perceive mechanical signals through multiple pathways, including Piezo1, transient receptor potential vanilloid 4 (TRPV4) mechanically sensitive channels, the integrin family of mechanotransduction receptors, and podosomes on the cell body. These pathways promptly initiate intracellular Ca² fluctuations and promote the Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) for their nuclear translocation, as well as induce other mechanisms, generating a cascade reaction to activate macrophages. After activation, macrophages effectively recruit neutrophils and monocytes by coordinating the chemokine network and dominate the resolution of inflammation and the initiation of tissue repair via dynamic polarization between M1 and M2 phenotypes. Additionally, they regulate T cell-mediated adaptive immune responses through antigen presentation and other means, and collaborate with fibroblasts to promote the remodeling and repair of the ECM. This article focuses on providing a systematic perspective on the cellular and molecular basis of acupuncture initiation through the response of macrophages to acupuncture signals and their regulation of the immune network.

Background: Recombinant Vesicular Stomatitis Virus (rVSV) vector vaccines have become essential in combating emerging viral diseases and have shown promise in immunotherapy, particularly in the discipline of cancer treatment. Although extensive research has been conducted in this rVSV field, a comprehensive bibliometric and landscape analysis is lacking.

Objective: To depict the current research landscape of recombinant vaccines and antitumor agents based on the VSV vector, especially of the critical focus areas, emerging trends, and ongoing clinical trials.

Methods: The software CiteSpace was used to conduct the bibliometric analysis to visualize rVSV research trends, prominent authors, leading institutions, contributing countries, frequently used keywords, and the top 10 most cited articles. Additionally, the advancements and research directions were explored by analyzing active clinical trials related to the rVSV field.

Results: A total of 311 publications from 1996 to 2024 were screened out from the Web of Science Core Collection based on predefined inclusion criteria. The cumulative annual publication volume showed a steady increase, with the United States and Canada leading in research output. Notable authors such as Heinz Feldmann and John K. Rose were identified as the most frequently cited contributors. Key cluster and reference analyses revealed a shift from studying basic mechanisms to focusing on vaccine construction and clinical trials. Furthermore, efficient trials were identified in both infectious disease vaccines and antitumor agents, providing insights into potential applications in the indication expansion of currently applied vaccines and precise targeting strategies in newly developed tumor agents.

Conclusion: Benefited by the CiteSpace-generated bibliometric analysis, this study mapped the evolution of research and highlighted key topics in rVSV vaccine development. The comprehensive review of recent advancements and active clinical trials (using clinicaltrial.gov) offers valuable insights into current trends and future research directions.

A patient with myelodysplasia received a haploidentical hematopoietic stem cell transplant (HCT). Pre-transplant HLA antibody screening showed no detectable donor-specific antibodies (DSAs). Post-transplant, the patient developed an anti-HLA-A2 antibody, likely due to a memory B-cell response. This immune response led to platelet transfusion refractoriness and graft failure. The patient engrafted following a second stem cell infusion from the same haploidentical donor, using both HLA compatible platelets, to support initial platelet transfusion refractoriness (PTR) following primary stem cell infusion, and HLA-A*02 expressing platelets, to adsorb the circulating anti-A2 prior to the re-infusion.

[This corrects the article DOI: 10.3389/fimmu.2025.1734346.].

Pulmonary light chain deposition disease (PLCDD) is a rare disorder characterized by the deposition of immunoglobulin light chains in the lungs, often associated with lymphoplasmacytic proliferative and autoimmune disease such as primary Sjögren disease (pSjD). Due to its rarity, there is currently no established definitive management of PLCDD. In this case report, we present the clinical presentation of a 42-year-old female with a history of pSjD who experienced recurrent hemoptysis over a period of 3 years. Radiological and pathological assessments confirmed pulmonary involvement of light chain deposition disease. Despite initial failure of glucocorticoids and immunosuppressive agents in targeting pSjD, subsequent combination therapy with bortezomib and dexamethasone (BD) resulting in significant clinical and radiological improvement. The successful use of this combination treatment in PLCDD represents a significant breakthrough, highlighting the potential effectiveness of targeted therapies for PLCDD secondary to autoimmune disease.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment landscape for malignant tumors such as advanced lung cancer, but their efficacy is limited. In recent years, the circadian rhythm has provided a brand-new optimization strategy for immunotherapy. This perspective article aims to explore the potential mechanisms of the interaction between immunotherapy and circadian rhythms, reviews clinical evidence supporting that "time-of-day receipt of ICIs brings better therapeutic effects", and conduct an in-depth analysis of the current practical challenges of chrono-immunotherapy. And emphasize the potential of "chrono-immunotherapy" as a valuable therapeutic approach.