Inflammation Research最新文献

Background: Lung disease remains a leading cause of global morbidity and mortality, with prevalence strongly influenced by lifestyle factors, including dietary patterns such as the Western diet. Chronic lung inflammation, driven by dysregulated immune responses, is a hallmark of many pulmonary conditions and exacerbates disease progression and severity Emerging evidence highlights potentially critical role of for Dietary fibre and it's metabolites particularly short chain fatty acids (SCFAs), acetate, butyrate and propionate, in modulating the gut-lung axis and regulating pulmonary immune response.

Objective: This review summarizes current evidence on how dietary fibre and SCFAs influence pulmonary immunity and inflammation through systemic and local mechanisms.MethodsLiterature on dietary fibre intake, SCFA production, and immune regulation in the context of lung disease was reviewed to identify key effects and mechanistic insights.

Findings: SCFAs, including acetate, butyrate, and propionate, are produced by gut microbial fermentation of fibre and act via G-protein coupled receptor signalling and histone deacetylase inhibition. These metabolites modulate epithelial and immune cell function, reduce inflammation, and enhance lung immune protection. Beyond local effects, SCFAs influence hematopoietic cells in the bone marrow, altering their recruitment and activity in the lung.

Conclusions: Dietary fibre intake and SCFA-mediated gut-lung immune regulation represent a promising area for therapeutic development. A deeper understanding of these pathways may support novel strategies for the prevention and treatment of respiratory diseases.

Objective: Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a significant global health burden, characterized by complex host-pathogen interactions that drive heterogeneous clinical outcomes. While pulmonary epithelial cells are increasingly recognized as active participants in innate immunity during Mtb infection, how host defense are altered when the epithelial barrier is compromised remains unclear.

Methods: In this study, we developed a murine model combining naphthalene-induced pulmonary epithelial injury with Mtb infection and mapped the pulmonary cells landscape through single-cell RNA sequencing (scRNA-seq), followed by in vitro stimulation assays to validate macrophage functional changes.

Results: Notably, we found a pronounced impairment in pulmonary bacterial clearance. Transcriptomic analysis revealed a widespread suppression of epithelial immune functions and showed that macrophages transitioned from an antimicrobial to an antigen-presenting phenotype, indicating waning pulmonary innate defenses and heightened adaptive immune activation. In vitro experiments further suggested that this macrophage transition may be linked to epithelial cell alterations.

Conclusions: These findings indicate that pulmonary epithelial integrity may influence early host immune responses to Mycobacterium tuberculosis and provide a transcriptomic framework for exploring epithelial-immune crosstalk as a potential therapeutic target.

Objective and design: The objective was to determine the association between serum IgE levels and the infiltration order of T lymphocytes and macrophages in pancreatic islets in relation to the loss of insulin and glucagon cells in presymptomatic congenic BB Gimap5-DP (Diabetes Prone) rats.

Material: Congenic prediabetes BB Gimap5-DP and control Gimap5-DR (Diabetes Resistant) rats were followed every other day from 29 to 32 days of age until peak serum IgE (≤ 55 days of age).

Methods: Serum IgE was measured using ELISA. The HALO™ platform facilitated quantitative image analysis of infiltrating T lymphocytes, macrophages, and target organ insulin and glucagon cells. Whole genome sequencing (WGS) was employed to identify candidate type 1 diabetes genes.

Results: Serum IgE levels increased with age in normoglycemic BB Gimap5-DP rats. Quantification of infiltrating cells per mm² in and around the islets indicated that T lymphocytes are the initial infiltrators, followed by macrophages. Elevated serum IgE levels inversely correlated with beta-cell mass (total mg insulin/mg pancreas). WGS refined the risk segment for islet inflammation to 1.02 Mbp, leaving 10 candidate genes, including Gimap4 and Gimap5.

Conclusions: Elevated IgE levels herald T lymphocyte and macrophage infiltration. Pancreatic islet inflammation was linked to Gimap4, Gimap5, and other potential candidate genes on rat chromosome 4.

Objective: Hypertension remains a global health crisis, with conventional therapies failing in 40% of patients. Renal denervation (RDN) has emerged as a promising therapeutic alternative for resistant hypertension; however, the mechanisms underlying its antihypertensive effects remain unclear. Ifi27l2a, an interferon-stimulated gene, is implicated in neuroinflammatory processes. Therefore, we investigated the hypertensive mechanisms of RDN, focusing on its effects on Ifi27l2a expression.

Methods: Cells from the single-cell RNA sequencing datasets were analyzed via clustering and cell type identification to delineate microglial populations impacted by RDN. In vivo experiments were conducted to validate changes in Ifi27l2a expression and cyclic GMP-AMP synthase (cGAS)-STING pathway activation. In vitro, siRNA-mediated Ifi27l2a knockdown in BV2 microglia was employed to evaluate its effects on cGAS-STING pathway activation and cytokine release.

Results: Single-cell RNA sequencing revealed significant Ifi27l2a downregulation in microglia following RDN. In vivo, cGAS-STING signaling was significantly downregulated, as indicated by decreased cGAS, p-STING, and p-IRF3 expression, which correlated with attenuated neuroinflammatory responses. In vitro validation with Ifi27l2a-knockdown BV2 cells demonstrated coordinated downregulation of inflammatory cytokines and attenuated cGAS-STING pathway activity, confirming its regulatory role in neuroinflammation.

Conclusions: Ifi27l2a is a crucial link between RDN and neuroinflammation resolution, offering a therapeutic target for resistant hypertension.

Objective and design: This study aimed to investigate the role of pyruvate kinase muscle isoform 2 (PKM2) in macrophage-driven allergic rhinitis (AR) pathogenesis using both in vivo and in vitro experimental models.

Material or subjects: Myeloid-specific PKM2 knockout (PKM2^mye-KO) and littermate control (PKM2^WT) mice were used, along with human nasal mucosa samples from AR patients and bone marrow-derived macrophages (BMDMs).

Treatment: BMDMs were treated with the PKM2 activator TEPP-46 (100 µM) or vehicle prior to house dust mite (HDM) stimulation.

Methods: Histological and immunological analyses were performed on human and murine tissues. Cytokine expression, nuclear translocation, and metabolic markers were assessed in BMDMs following HDM stimulation. Statistical significance was evaluated using appropriate tests (e.g., Student's t-test or ANOVA).

Results: PKM2 levels and macrophage infiltration were elevated in AR patient nasal mucosa. PKM2^mye-KO mice showed reduced allergic inflammation, decreased pro-inflammatory cytokines (e.g., IL-6, TNF-α), and suppressed STAT3 activation compared to controls. TEPP-46 treatment attenuated HDM-induced cytokine release and nuclear PKM2 translocation.

Conclusions: PKM2 regulates macrophage-mediated inflammation in AR via STAT3-dependent pathways, suggesting its nuclear translocation and interaction with STAT3 as potential therapeutic targets for allergic diseases.

Background: Endothelial dysfunction is considered to play a pivotal role in the pathogenesis of preeclampsia (PE). Transcutaneous auricular vagus nerve stimulation (taVNS) is a potential non-pharmaceutical alternative treatment for PE. This study aimed to explore the mechanisms of taVNS on endothelial dysfunction.

Methods: We used the reduced uterine perfusion pressure method to establish PE model and TNF-α to establish endothelial dysfunction model in HUVECs. In vivo, we detected blood pressure, vascular proteomics and morphology, ACh and receptor α7nAChR, and inflammatory factors (IL-6, IL-1β, and TNF-α). In vitro, we checked cell viability, mitochondrial membrane potential, apoptosis rate, calcium levels, HUVECs morphology, and Endoplasmic reticulum (ER) and mitochondria (MITO) interaction.

Results: taVNS promoted the release of ACh, which decreased Ca²⁺ inflow from ER to MITO through the IP3R1/GRP75/VDAC1 complex, presumably through α7nAChR. This reduced the release of pro-apoptotic proteins (cleaved caspase-3, HSC70, and cytochrome C) and helped preserve the morphological and functional integrity of mitochondria, thus reducing the apoptosis of HUVECs, improving endothelial function, and relieving PE.

Conclusion: taVNS may exert an anti-PE effect through ER-MITO interaction. These findings offer preliminary insights into PE pathogenesis, and suggest that the ACh/α7nAChR axis and IP3R1/GRP75/VDAC1 complex could be promising targets for future therapeutic investigation.

This correspondence comments on the recent review "Exosomes as immunomodulators in autoimmune inflammation: implications for primary Sjögren's disease," emphasizing the dual role of exosomes in primary Sjögren's disease (pSD). On one side, lymphocyte-derived vesicles contribute to epithelial dysfunction through pathogenic microRNA transfer; on the other, mesenchymal stromal cell-derived exosomes show promising immunomodulatory and regenerative properties. Salivary and tear-derived exosomes emerge as attractive diagnostic tools, although their clinical adoption remains hindered by methodological variability. The discussion extends to systemic involvement, including pulmonary hypertension and cardiovascular risk, highlighting exosomes as potential predictive biomarkers. Overall, the letter underscores the translational opportunities of exosome research in pSD while calling for advances in standardization, targeted delivery, and large-scale production to facilitate clinical integration.

Background: Traumatic spinal cord injury (SCI) is a severe clinical challenge, often leading to long-term sensory, motor, and autonomic dysfunction. The SCI cascade involves a primary physical damage phase, followed by a secondary phase of inflammatory signalling driven by microglia and other infiltrating immune cells. Immunomodulatory therapies may help promote healing and restrict secondary damage. We have previously demonstrated that interleukin (IL)-13 delivery improves functional and histopathological recovery after SCI in murine models, primarily by polarising macrophages towards an alternatively activated pro-reparative M2-like phenotype and reducing axonal contacts. Although microglia respond robustly to IL-13 in vitro, polarisation of microglia in vivo is more difficult. To better understand what conditions may restrict microglial responses to IL-13 in vivo, we sought to examine the effect of cellular context or microenvironment on IL-13 efficacy in forcing microglia polarisation in vitro.

Methods: BV2 and murine induced pluripotent stem cell (miPSC)-derived microglia were treated with IL-13 alone or in combination with lipopolysaccharide (LPS), acidic media, extracellular matrix components, high glutamate or high potassium concentrations. Following this phenotypic changes including morphology, gene/protein expression (TNFα, IL-1β, iNOS, Arg-1, CD206, F4-80) and cytokine release (TNFα) were measured using high-content screening, RT-qPCR, immunohistochemistry, and ELISA.

Results: IL-13 leads to increased expression of the anti-inflammatory marker Arg-1 while lowering expression and secretion of the pro-inflammatory markers IL-1β, iNOS, and TNFα, and expression of the microglia activation marker F4-80, signifying effective polarisation of microglia. Concomitant administration of LPS with IL-13 reduces IL-13 polarisation efficacy in microglia. Forced polarisation of microglia is also compromised by high glutamate tone, acidosis, hyperkalemia, and extracellular fibronectin, suggesting microenvironmental contexts seen in neurotrauma directly act on microglia to limit polarisation potential.

Conclusions: Our study demonstrates that the post-SCI environment dampens IL-13 efficacy on microglia. Taken together these data caution against simple immunomodulatory strategies and suggest that effective polarisation of microglia in vivo will require multimodal approaches.

Background: Long COVID is a debilitating illness with multi-systemic symptoms that affects at least 10% of individuals who have had COVID-19. Symptoms include respiratory, dermatological, gastrointestinal, cardiovascular, and most frequently reported, neurological sequelae. The most common neurological manifestations include fatigue, brain fog, memory issues, attention disorder, and headaches.

Methods: In this review, we explore the current literature and highlight key findings regarding not only the clinical presentations of neurological commitment during long COVID but mainly the mechanisms that culminate in neuroinflammation, such as autoimmunity, viral reservoirs, and lack of surveillance of T-cells.

Results: Neuroinflammation is a complex multicellular response that directly impacts microglial cells and includes inflammasome activation, trafficking of immune cells, and increased circulating autoantibodies, cytokines, and chemokines in the central nervous system, directly impacting the tissue homeostasis. This review provides important information beyond the clinical manifestations of long COVID. Here, we highlight multifactorial neuroinflammation as the main mechanism involved in long COVID, bringing together several studies that address the different mechanisms that culminate in inflammation of the central nervous system, and highlight possible biomarkers involved in this syndrome and potential therapeutic approaches that have been studied.

Conclusion: Thus, this review strengthens research into long COVID and provides new possibilities for future studies.

Itaconate, a mitochondrial metabolite generated from cis-aconitate via IRG1 (ACOD1), has emerged as a key immunometabolic signal that links metabolic reprogramming with immune regulation. Beyond its origin in the tricarboxylic acid (TCA) cycle, itaconate exemplifies how metabolic intermediates can reshape cell fate and function under stress and inflammation. Upon inflammatory stimulation, immune cells-particularly macrophages-undergo profound metabolic rewiring. Itaconate orchestrates this shift by inhibiting succinate dehydrogenase (SDH), accumulating succinate, activating nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant responses, and modulating glycolytic flux, thus balancing inflammatory output and oxidative stress. This review provides an integrative overview of itaconate biosynthesis, metabolic regulation, and functional mechanisms across diverse physiological and pathological contexts. Itaconate and its derivatives, such as 4-octyl itaconate (4-OI), exhibit promising effects in preclinical models of sepsis, acute lung injury, autoimmune diseases (e.g., SLE and RA), ischemia-reperfusion injury, infection (bacterial and viral), and cancer. These effects are closely linked to itaconate's capacity to reprogram immune metabolism and modulate signaling pathways such as NF-κB, NLRP3, and JAK/STAT. Importantly, recent findings suggest that itaconate not only modulates inflammation but also affects immune cell death pathways, ferroptosis susceptibility, and tumor immune evasion. These multifaceted roles make itaconate a potential metabolic checkpoint in the development of new therapeutic strategies. However, challenges such as metabolic instability, limited bioavailability, and potential off-target effects remain to be addressed. In summary, itaconate represents a powerful endogenous modulator of immunometabolism. Its therapeutic utility, as a direct drug, as a scaffold for derivative design, or as a biomarker for inflammation resolution, holds significant promise for treating inflammation-driven diseases through the lens of metabolic reprogramming. This review summarizes itaconate biosynthesis, its molecular mechanisms in health and disease, and recent advances across multiple conditions, providing a foundation for future immunometabolic therapies.