Search Results (12,194)

Inflammatory bowel disease (IBD) is characterized by intestinal barrier dysfunction and excessive inflammation, in which STAT3 signaling plays a critical role. Berberine is clinically effective against colitis; its application is limited by low bioavailability and toxicity. Berberrubine, a major metabolite of berberine, exhibits improved pharmacological properties; however, its therapeutic potential in IBD remains unclear. The efficacy and mechanisms of berberine and berberrubine were evaluated in DSS-induced colitis mice, LPS-stimulated cells and intestinal organoids. STAT3 knockout cell lines were generated using CRISPR-Cas9 to assess the role of STAT3 in mediating the pharmacological activities of both compounds. We found that berberrubine significantly alleviated colitis, reduced pro-inflammatory cytokines (IL-6 and TNF-α), and restored intestinal barrier integrity by upregulating ZO-1 and claudin-1 in vivo and in organoids, demonstrating superior efficacy and safety to berberine. Mechanistically, both compounds inhibited STAT3 activation and nuclear translocation. STAT3 deficiency attenuated their anti-inflammatory, anti-tumor, and barrier-protective effects. Notably, berberrubine exhibited selective cytotoxicity to cancer cells over normal epithelial cells, suggesting a favorable therapeutic window. Collectively, berberrubine ameliorates intestinal barrier dysfunction and inflammation through inhibition of the STAT3 signaling pathway. Its superior efficacy and favorable safety profile compared to berberine support its potential as a novel therapeutic agent for IBD. Full article

Deoxynivalenol (DON), a prevalent mycotoxin, induces intestinal and hepatic injury. Fructus mume extract (FME) possesses bioactive properties, yet its protective role against DON remains unclear. This study aimed to investigate the protective mechanisms of FME in DON-challenged mice. Male C57BL/6 mice were divided into control, DON (3 mg/kg), and DON with low-, medium-, or high-dose FME groups for 4 weeks. Analyses included histopathology, UPLC-Q-TOF-MS, network pharmacology, biochemistry, qRT-PCR, immunohistochemistry, a TUNEL assay, metagenomics, and metabolomics. FME significantly alleviated growth inhibition and tissue damage. Among the 38 components identified by UPLC-Q-TOF-MS, all 38 acted on 156 genes, including IL-1β, caspase3, and BAX, to alleviate DON-induced intestinal and hepatic injury. FME enhanced hepatic antioxidant capacity and reduced inflammation by suppressing NF-κB signaling. FME upregulated tight junction proteins, inhibited apoptosis, and restored microbial diversity by enriching beneficial bacteria. Metabolomics revealed FME reversed DON-induced metabolic disruptions in the liver. Correlation analysis indicated FME remodeled the microbiota–liver metabolite network. In conclusion, FME attenuates DON-induced intestinal injury by modulating the gut–liver axis through antioxidant, anti-inflammatory, and anti-apoptotic activities. Full article

Background: Skin photoaging, primarily induced by chronic ultraviolet (UV) radiation exposure, is characterized by dryness, wrinkle formation, pigmentation abnormalities, and reduced skin elasticity, resulting from oxidative stress, inflammation, and degradation of the extracellular matrix. Codonopsis pilosula, a traditional food–medicine homologous plant, is recognized for its anti-aging properties. However, its lipophilic components (designated as CP-L) remain insufficiently explored. Methods: Herein, we developed a thermosensitive nanogel encapsulating CP-L-loaded transferosomes (CP-L nanogel) to enhance topical delivery and evaluated its effects in both a UV-induced photoaging mouse model and UVB-irradiated HaCaT keratinocytes. Results: In UV-induced mice, topical application of the nanogel markedly reduced skin wrinkling and epidermal hyperplasia, with epidermal thickness decreased by 83.2% compared to the model group (p < 0.01), and restored skin elasticity and collagen deposition, as evidenced by a 35.5% increase in collagen area fraction (p < 0.01). Correspondingly, in UVB-irradiated HaCaT cells, it significantly increased cell viability from 53.0 ± 9.6% to 89.4 ± 1.0% (p < 0.01) and suppressed apoptosis from 30.1 ± 0.48% to 12.4 ± 0.66% (p < 0.01). Furthermore, the CP-L nanogel consistently attenuated oxidative stress, with SOD, CAT, and GSH-Px activities increased by 73.1%, 188.1%, and 18.2%, respectively (p < 0.01), and MDA levels reduced by 71.0% (p < 0.01), while inflammatory responses were suppressed, as TNF-α, IL-1α, IL-1β, and IL-6 levels decreased by 28.3%, 22.6%, 12.8% and 31.9%, respectively (p < 0.01). Mechanistically, transcriptomic and molecular analyses revealed that the nanogel potently inhibited the UV-induced activation of the FGFR/PI3K/AKT/mTOR/p70S6K signaling cascade at both transcriptional and protein levels, with the phosphorylation levels of FGFR, PI3K, AKT, mTOR, and p70S6K significantly reduced by 43.9%, 30.9%, 38.8%, 34.9%, and 57.3%, respectively (p < 0.01). Molecular docking and dynamics simulations identified isofuranodienone and aromadendrene oxide-(2) as key constituents with high-affinity, stable binding to FGFR1 and AKT1. The cytoprotective effect of the nanogel was completely abolished by co-treatment with the FGFR inhibitor PD173074, confirming functional reliance on this pathway. Enhanced cellular delivery of the formulation was directly demonstrated by flow cytometry, showing an approximately 1.8-fold increase in cellular uptake compared to the free drug (p < 0.01). Conclusions: Collectively, these results demonstrated that the CP-L nanogel alleviated skin photoaging through a multi-faceted mechanism involving enhanced cellular delivery, potent antioxidant and anti-inflammatory activities, and specific inhibition of the FGFR/PI3K/AKT/mTOR signaling cascade, highlighting its potential as a multitargeted topical agent derived from an edible plant. Full article

Aim: To evaluate the real-world effectiveness, durability, and safety of faricimab 6 mg in eyes with treatment-refractory retinal vein occlusion (RVO)-associated macular oedema (MO) in the United Kingdom (UK). Methods: This was a retrospective, single-centre observational study of eyes with RVO that were switched to faricimab after prior treatment with previous anti-vascular endothelial growth factor (anti-VEGF) agents. Baseline demographics, treatment history, pinhole visual acuity (VA), optical coherence tomography (OCT) biomarkers, and injection intervals were recorded. Eyes were treated using a treat-and-extend regimen without a loading phase. Functional, anatomical, durability, and safety outcomes were assessed over follow-up. Results: A total of 22 eyes from 22 patients were included, with a mean (SD) age of 67.9 (11.9) years and a mean (SD) RVO duration of 201.4 (153.1) weeks. Eyes had received a mean (SD) of 20.8 (16.9) prior anti-VEGF injections. The mean (SD) follow-up was 45.7 (15.8) weeks, with a mean (SD) of 5.9 (2.3) faricimab injections. There was no significant change in pinhole VA (53.5 (18.5) vs. 55.0 (18.8) letters, p = 0.08). The central subfield thickness (CST) reduced from 407.6 (102.1) to 377.0 (186.5) µm, and the maximum central retinal thickness from 483.6 (103.1) to 442.2 (187.2) µm, although these changes were not statistically significant (p > 0.05). The proportion of eyes with subretinal fluid (SRF) decreased from 18.2% to 4.5%, and intraretinal fluid (IRF) from 100% to 81.8%. Injection intervals between the first and second faricimab injections increased significantly from 4.9 (1.4) to 7.7 (3.4) weeks (final injection interval, p = 0.004). Six eyes (27.3%) discontinued faricimab, with three (13.6%) requiring an intravitreal dexamethasone implant following a suboptimal response. One eye (4.5%) developed transient intraocular pressure elevation; no cases of intraocular inflammation or endophthalmitis were observed. Conclusions: In this heavily pre-treated, chronic RVO cohort, switching to faricimab without a loading phase resulted in stable visual acuity, modest but non-significant anatomical improvements, and a significant extension in treatment intervals. These findings suggest that faricimab may provide durability benefits and disease stabilisation in treatment-refractory RVO, although functional gains may be limited in chronic disease. Further prospective studies are required to define optimal switching strategies. Full article

Metabolic syndrome (MetS) is a major driver of cardiovascular disease, renal injury, and hepatic steatosis, largely through chronic low-grade inflammation and oxidative stress. This study evaluated the cardioprotective, nephroprotective, and hepatoprotective potential of a polyphenol-rich fraction (PP) isolated from Ilex aquifolium leaves in obese Zucker (fa/fa) rats—a well-established model of MetS. Male rats (8 weeks old) were randomly assigned to receive either a standard diet (CTRL, n = 8) or the same diet supplemented with 10 mg/kg body weight/day of the polyphenol fraction (PP, n = 8) for 8 weeks. The fraction was dominated by chlorogenic acid (59.33 mg/g), neochlorogenic acid (35.39 mg/g), and rutin (9.23 mg/g). At the end of the experiment, biochemical markers of oxidative stress, inflammation, and metabolic status were assessed, together with detailed histopathological examination of the heart, kidneys, and liver. Supplementation with Ilex aquifolium polyphenols significantly increased (p < 0.01) total antioxidant status, reduced circulating IL-6 and increased MCP-1 levels. These changes were accompanied by clear cardioprotective effects. However, the intervention also produced organ-specific adverse effects. In the kidneys, polyphenol-treated rats exhibited histopathological features consistent with early-stage nephropathy. In the liver, supplementation exacerbated hepatic steatosis compared to controls. In conclusion, the polyphenol-rich fraction from Ilex aquifolium exerts potent antioxidant and anti-inflammatory effects that translate into substantial cardioprotection in obese Zucker rats. Nevertheless, its capacity to worsen renal injury and hepatic steatosis highlights the need for caution and further dose- and duration-dependent studies before considering therapeutic application in metabolic syndrome. Full article

Background: Eugenia involucrata DC. is a Brazilian native species of the Myrtaceae family traditionally used in folk medicine and known for its antimicrobial, antifungal, and antioxidant properties. However, its anti-inflammatory potential remains poorly investigated. Methods: This study characterized the essential oil from E. involucrata leaves and evaluated its anti-inflammatory activity using in vitro and in vivo models. The chemical composition was determined by gas chromatography–mass spectrometry (GC–MS). Anti-inflammatory activity was assessed in LPS-stimulated RAW 264.7 macrophages and in murine paw edema models induced by carrageenan, compound 48/80, bradykinin, and prostaglandin E₂. Results: GC–MS analysis identified 23 compounds, representing 91.41% of the oil composition, with predominance of oxygenated sesquiterpenes. The major constituents were globulol (15.71%), α-selinene (13.14%), selin-11-en-4-α-ol (8.31%), cubeban-11-ol (8.04%), and β-elemene (6.78%). The essential oil showed no significant cytotoxicity below 100 micrograms/mL toward RAW 264.7 macrophages and significantly reduced LPS-induced TNF-α and IL-1β gene expression. In vivo, it markedly inhibited paw edema induced by carrageenan, compound 48/80, and bradykinin, but not by prostaglandin E₂. Conclusions: These findings demonstrate that E. involucrata essential oil possesses significant anti-inflammatory and anti-edematogenic activity, likely through modulation of early inflammatory mediators involved in acute inflammation. Full article

Chronic Obstructive Pulmonary Disease (COPD) is a chronic respiratory condition characterized by progressive deterioration in lung function and persistent symptoms, particularly dyspnea, which can lead to death. Inflammation is important in COPD pathogenesis because it causes persistent inflammatory responses in the respiratory tract. Therefore, this study aimed to investigate H₂O extracts derived from Wedelia (Sphagneticola trilobata) and Sembung Rambat (Mikania micrantha), respectively, as anti-inflammatory agents and to analyze the metabolite profiles contained in the extracts. The results showed that Sembung Rambat H₂O extract demonstrated significant inhibition of IL-2 (100 ± 0.00%), while Wedelia extract inhibited 74.68 ± 7.13% release of pro-inflammatory cytokine IL-6. Liquid Chromatography–Tandem Mass Spectrometry (LC-MS/MS) analysis mainly identified the presence of amino acids, phenolic acids, organic acids, and terpenoids in both extracts. These results suggest the promising potential of Wedelia and Sembung Rambat extracts as herbal therapy for COPD. Full article

Background: Doxorubicin is an effective antineoplastic agent, but its use is constrained by off-target toxicities, including acute liver injury driven by mitochondrial dysfunction, oxidative stress, sterile inflammation, and redox-sensitive signaling pathways. Exenatide, a glucagon-like peptide-1 receptor agonist, exerts antioxidant and anti-inflammatory effects in several experimental liver injury models, but its role in doxorubicin-induced hepatic injury has not been investigated to our knowledge. This study evaluated whether exenatide attenuates acute doxorubicin-induced hepatic injury and examined whether the observed biochemical changes are consistent with modulation of oxidative stress and SIRT1–HMGB1/NF-κB-related signaling. Methods: Male Wistar albino rats were allocated to four groups (n = 7/group): control, exenatide, doxorubicin, and exenatide + doxorubicin. Exenatide (10 µg/kg/day, intraperitoneally) was administered for seven days. Doxorubicin was given intraperitoneally on days 5–7 at a cumulative dose of 18 mg/kg. The pretreatment design was used to test preventive attenuation rather than reversal of established injury. Hepatic injury-associated enzyme activities, serum HMGB1, hepatic SIRT1, NF-κB, TNF-α, IL-6, IL-10, malondialdehyde, glutathione, total antioxidant status, total oxidant status, nitric oxide, and hepatic ^99mTc-pyrophosphate uptake were assessed. Results: Doxorubicin substantially increased intrahepatic ALT and AST activities, serum HMGB1, hepatic NF-κB, TNF-α, IL-6, malondialdehyde, total oxidant status, nitric oxide, and hepatic ^99mTc-pyrophosphate uptake, while reducing SIRT1, IL-10, glutathione, and total antioxidant status. Relative to the doxorubicin group, exenatide lowered HMGB1 by 48.3%, hepatic ^99mTc-pyrophosphate uptake by 48.7%, malondialdehyde by 45.0%, total oxidant status by 37.3%, nitric oxide by 40.7%, NF-κB by 40.4%, TNF-α by 48.6%, and IL-6 by 41.1%, while increasing SIRT1 by 91.7%, IL-10 by 115%, glutathione by 115%, and total antioxidant status by 87.8%. None of the altered parameters returned completely to control levels, indicating attenuation rather than full normalization of acute injury-related changes. Conclusions: Exenatide attenuated doxorubicin-induced acute hepatic injury in this rat model and was associated with reduced oxidative stress, reduced inflammatory activation, higher hepatic SIRT1 levels, lower serum HMGB1 levels, and reduced hepatic ^99mTc-pyrophosphate uptake. The findings are consistent with involvement of SIRT1–HMGB1/NF-κB-related signaling, but they do not establish causality. Hepatic ^99mTc-pyrophosphate uptake should be interpreted as an exploratory imaging correlate of tissue injury rather than an established liver biomarker. Additional studies incorporating histopathology, immunohistochemistry, functional liver indices, mechanistic validation of SIRT1, and tumor-bearing models are required before translational conclusions can be drawn. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) represents the hepatic manifestation of systemic metabolic dysfunction and has emerged as one of the leading causes of chronic liver disease worldwide. Its pathogenesis is complex and multifactorial, involving insulin resistance, altered lipid metabolism, mitochondrial dysfunction, oxidative stress, and chronic low-grade inflammation. Beyond these classical mechanisms, growing evidence highlights the central role of modifiable lifestyle-related factors, including chronic positive energy balance, high intake of fructose and saturated fats, ultra-processed foods, physical inactivity, sleep disruption, and environmental exposures such as endocrine-disrupting chemicals and air pollution, which have been associated with the activation of lipogenic and proinflammatory pathways in preclinical and observational studies. Conversely, protective dietary patterns, particularly the Mediterranean diet, together with regular physical activity, exert hepatoprotective metabolic and anti-inflammatory effects. An extensive literature search was conducted across the PubMed, Scopus, Cochrane Library, and Embase databases, covering publications through June 2026. The review was conducted following the SANRA recommendations for narrative reviews. The inclusion criteria encompassed clinical trials, systematic reviews, meta-analyses, and international clinical practice guidelines. This review provides an integrated framework by linking in a single interpretative model the classical pathogenic pathways with emerging dietary, behavioral, and environmental determinants and with systemic interorgan communication networks involving hepatokines, adipokines, and myokines. Understanding MASLD as a multisystemic metabolic disease driven by multiple determinants has critical implications for the development of targeted preventive and therapeutic strategies aimed at reducing its global burden and prevalence. Full article

Older adults and individuals with chronic obstructive pulmonary disease (COPD) are vulnerable to the harmful health effects of fine particulate matter (PM_2.5), which are partly driven by systemic inflammation. This study examined whether older adults with COPD exhibit greater inflammatory responses to PM_2.5 than age-matched healthy controls. We compared circulating high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-alpha in 38 patients with COPD (73.6 ± 7.1 years) and 20 controls (70.9 ± 5.2 years) during high- and low-pollution periods. In the COPD group, 65.8% used inhaled corticosteroids and 42.1% used statins; 65.0% of controls used statins. Mean PM_2.5 concentrations were higher in the high-pollution period than the low-pollution period (79.1 ± 23.3 vs 13.9 ± 3.6 µg/m³; p < 0.001). Across both periods, IL-8 was higher in COPD than in controls, without significant within-group increases during high pollution. These findings indicate higher baseline systemic inflammation in COPD, while pollution-associated increases may be attenuated by anti-inflammatory medications. However, this should be interpreted cautiously given the observational design. Full article

Natural products have long contributed to oncology by providing structurally diverse metabolites and pharmacologically relevant scaffolds. Despite advances in precision oncology, immunotherapy, and targeted therapies, cancer remains a leading cause of morbidity and mortality worldwide. Plant-derived metabolites continue to attract attention due to their ability to modulate key processes such as apoptosis, metabolic adaptation, epigenetic regulation, oxidative stress, inflammation, and tumor microenvironment signaling. However, current evidence is heterogeneous and often based on simplified in vitro models or insufficiently characterized extracts. This review critically distinguishes pharmacologically validated findings from preliminary claims with limited translational relevance. A narrative synthesis of global advances was conducted, focusing on mechanistic pathways, major phytochemical classes, and emerging technologies shaping compound discovery and preclinical validation. The potential contribution of Chilean biodiversity was also examined. Although several Chilean plant species demonstrate cytotoxic, anti-inflammatory, and antioxidant activities relevant to oncology, most findings remain preclinical, limited by inadequate taxonomic identification, lack of phytochemical standardization, scarce in vivo validation, and insufficient pharmacological characterization. The future impact of natural products on oncology will depend on stricter standards for chemical characterization, biological validation, and translational relevance. Chilean biodiversity represents a promising yet largely prospective source for cancer-related drug discovery. Full article

Background: MASLD is a disorder linked to lipid metabolism and obesity, increasingly prevalent among sedentary people and leading to hepatic fibrosis. Cyclodipeptides (CDPs) have promising anti-obesogenic and liver-protective potential. Methods: CDP treatment was evaluated in a chronic MASLD model using female Wistar rats fed an obesogenic diet, with assessments of insulin resistance, glucose tolerance, liver damage, oxidative stress, and the expression of genes related to metabolic function. Results: MASLD CDP-treated rats showed low visceral adipose tissue (VAT) content, improved insulin responsiveness and glucose tolerance, reduced steatosis, and reversed oxidant stress and the NRF2, GPX1, and GCLC expression. Furthermore, MASLD-related dysregulation of genes involved in lipid metabolism was restored, including vLDL transport (MTTP, APOB, and RASAL2), β-oxidation (PPAR-α, ACOX1, and FOXO1), lipogenesis (ACC1 and SREBP 1C), and fatty acid transport (PSD3 and CD36). In accordance, genes of key signaling pathways were also restored, including mTOR, TSC1, and TSC2, along with fibrosis and inflammation TGF-β, Fas, NF-κB, and IL-6. In VAT of MASLD animals, crown-like structures and adiposity density were diminished by CDP treatment, with increased expression of genes associated with beige-like adipose tissue remodeling, including PGC-1α, UCP1, NRF1, ATP6v1, CEBP-α, COX4i1, PPARγ, and CS. Consistently, the UCP1 and PGC-1α protein expression was increased in the VAT of MASLD animals treated with CDPs. Conclusions: The anti-MASLD effects of CDPs were associated with reversal of key pathogenic markers in the liver and VAT, suggesting remodeling of white adipose tissue (WAT) toward a beige-like adipose tissue phenotype. The findings suggest that CDPs may modulate adipose tissue structure and adipogenesis, underscoring their therapeutic relevance for MASLD. Full article

Implant-associated infections (IAIs) caused by Staphylococcus aureus are a major cause of orthopedic implant failure, driven by biofilm formation and chronic inflammation. Macrophages regulate bacterial clearance and tissue repair through polarization into pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes. This systematic review evaluated preclinical in vivo studies according to PICO criteria (Population: IAI animal models; Intervention: functionalized biomaterials; Comparator: non-functionalized controls; Outcome: bacterial burden reduction associated with macrophage reprogramming). A PRISMA-guided search of PubMed, Scopus, Web of Science, and Embase (January 2015–December 2025) identified 23 eligible studies, assessed using SYRCLE’s risk-of-bias tool. Due to heterogeneity, a narrative synthesis was performed without meta-analysis. Effect measures included bacterial CFU reduction, macrophage polarization markers, cytokine expression, and histological outcomes. In 87.5% of studies, macrophage modulation was associated with reduced bacterial load, biofilm disruption, and improved peri-implant tissue repair and bone integration. These findings support immunomodulatory biomaterials as promising strategies to manage IAIs through combined antibacterial and immune-regulatory mechanisms. However, further validation in larger animal models is required, particularly for nanomaterials. The protocol of this systematic review was registered on the Open Science Framework. Full article

Background: Pharmacological blockade of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome has emerged as an attractive pharmacological strategy for a broad range of inflammatory and metabolic disorders. However, translating preclinical efficacy into clinical success remains a major bottleneck. We previously reported the discovery of a novel, potent NLRP3 inhibitor, KBD3536, but its in vivo efficacy across different pathological conditions remains uncharacterized. Here, we systematically evaluated the in vivo efficacy of KBD3536 across diverse preclinical models of NLRP3-related pathologies. Methods: KBD3536 was evaluated in established rodent models of monosodium urate (MSU)-induced acute inflammation (mouse air pouch and rat gouty arthritis models), radiation-induced dermatitis (RID), and high-fat diet (HFD)-induced obesity. Results: In the MSU models, KBD3536 markedly suppressed local interleukin-1β and interleukin-6 secretion in air pouch exudates and dose-dependently alleviated acute arthritis symptoms, including joint swelling and joint pain. In the RID model, KBD3536 significantly attenuated radiation-induced skin injury and ameliorated radiation-induced systemic weight loss. Under HFD challenge, early intervention with KBD3536 mitigated HFD-induced adiposity, early hepatic steatosis and its associated inflammatory responses, and preserved physical performance. Mechanistically, KBD3536 partially restored AMP-activated protein kinase α1 (AMPKα1) mRNA expression in adipose tissue and restored hepatic Cyp3a11 transcriptional activity. Conclusions: NLRP3 inhibitor KBD3536 exhibited broad-spectrum anti-inflammatory efficacy across multiple preclinical models, supporting its potential as a promising candidate for diverse NLRP3-related disorders. Full article

Allergic asthma is associated with a reduction in the number of regulatory T cells (Tregs). Although interleukin-27 (IL-27) has been shown to modulate Tregs potentially through the Lymphocyte-activation gene 3 (Lag3) pathway, the underlying mechanism remains incompletely defined. Objective: This study sought to determine whether IL-27 ameliorates airway inflammation in asthma by modulating Tregs in a Lag3-dependent manner. Acute asthma was induced in wild-type (WT) and Lag3 knockout (Lag3^−/−) mice through sensitization and challenge with house dust mite (HDM). A treatment group received intranasal recombinant IL-27 prior to challenges. In WT mice, IL-27 administration significantly attenuated airway inflammation, goblet cell hyperplasia, and total cell counts in bronchoalveolar lavage fluid (BALF), along with reduced levels of Th2 cytokines (IL-4, IL-5). It also upregulated T-bet (Th1) mRNA expression, downregulated GATA-3 (Th2) and RORγt (Th17) levels, and increased the proportions of CD4⁺ Foxp3⁺ Tregs, CTLA4⁺ Tregs, and Lag3⁺ Tregs in lung tissue. Conversely, in Lag3^−/− mice, the protective effects of IL-27 were completely abrogated, with no observed increases in Treg populations or suppression of Th2/Th17 immune responses. The anti-asthmatic effect of exogenous IL-27 is associated with increased Treg frequency and upregulation of inhibitory markers, with Lag3 serving as a pivotal target on Tregs. Full article