Progression from chronic hepatitis B (CHB) to cirrhosis is closely associated with immune dysregulation and altered cytokine signaling, yet effective noninvasive immune biomarkers remain limited. This study aimed to develop a peripheral blood mononuclear cell (PBMC)-based cytokine gene signature for predicting HBV-related cirrhosis. The GSE114783 microarray dataset was analyzed to identify differentially expressed genes between CHB and cirrhosis. Immune-related candidate genes were selected by integrating curated immune resources and the Kyoto Encyclopedia of Genes and Genomes cytokine-cytokine receptor interaction pathway. Least absolute shrinkage and selection operator regression and multivariable logistic regression were used to construct the predictive model. Receiver operating characteristic analysis, leave-one-out cross-validation, and nomogram development were performed to evaluate model performance and support clinical translation. Differential expression analysis identified 3169 genes distinguishing cirrhosis from CHB, from which 86 immune/cytokine-related genes were prioritized. LASSO selected a parsimonious 4-gene signature-CXCR1, IL11RA, IL13RA2, and CD19-capturing key immune axes relevant to chronic inflammation and fibrogenesis (chemokine receptor signaling, IL-11/IL-13 receptor pathways, and B-cell-associated immunity). The resulting model achieved an area under the curve (AUC) of 0.935 (95% CI, 0.882-0.988); at an optimal cutoff of 0.832, sensitivity was 88.6% and specificity 84.3%. LOOCV supported robust performance, and the nomogram demonstrated good agreement between predicted and observed risk. A PBMC-based immune cytokine-receptor gene signature (CXCR1/IL11RA/IL13RA2/CD19) provides a noninvasive tool for immunologically informed risk stratification of HBV-related cirrhosis and may support immune monitoring and early intervention strategies. Prospective, multicohort validation and mechanistic studies are warranted.

Interleukin-11 (IL-11) is implicated in epithelial dysfunction, fibroblast activation, tissue remodeling, and chronic inflammatory responses; however, the clinical value of circulating IL-11 in airway disease remains uncertain. This single-center retrospective exploratory observational study included 88 adults: 31 with allergic rhinitis, 15 with non-allergic asthma, 22 with allergic asthma associated with allergic rhinitis, and 20 healthy controls. Serum IL-11 concentrations were measured using a quantitative sandwich enzyme-linked immunosorbent assay. Between-group differences were assessed using the Kruskal-Wallis test followed by Holm-adjusted pairwise Mann-Whitney U tests. Associations with disease-specific ordinal clinical categories were evaluated using Spearman rank correlation, with GINA treatment Steps used for asthma phenotypes and ARIA severity categories for allergic rhinitis. Median IL-11 concentrations were 62.01 pg/mL in non-allergic asthma, 78.87 pg/mL in allergic rhinitis, 61.92 pg/mL in allergic asthma associated with allergic rhinitis, and 95.46 pg/mL in healthy controls. The primary global comparison was not statistically significant (H = 5.667, p = 0.129), and no pairwise comparison remained significant after Holm correction. Six measurements (6.8%) were below the assay detection limit; replacing these values with 4.0 pg/mL in a sensitivity analysis did not materially alter the global result (H = 5.671, p = 0.129). Serum IL-11 was not significantly associated with GINA treatment step in non-allergic asthma (rho = -0.170, p = 0.544) or allergic asthma associated with allergic rhinitis (rho = 0.052, p = 0.818), nor with ARIA severity category in allergic rhinitis (rho = 0.046, p = 0.805). In an exploratory analysis adjusted for age, sex, body-mass category, and current smoking status, IL-11 concentrations were lower in each clinical phenotype relative to healthy controls; given the modest group sizes and baseline imbalance, this finding was considered hypothesis-generating. Overall, the primary analysis did not demonstrate significant differences in circulating IL-11 across study groups, and serum IL-11 was not associated with disease-specific ordinal clinical categories. These findings do not support the use of a single serum IL-11 measurement as a stand-alone biomarker of airway disease phenotype or clinical category in this cohort and warrant confirmation in larger, prospectively characterized cohorts.

The liver has a remarkable regenerative capacity, but persistent injury caused by drugs, metabolic dysfunction, alcohol, and chronic inflammation can overwhelm this process and promote fibrosis and hepatocellular carcinoma. Interleukin-11 (IL-11), a cytokine that signals through glycoprotein 130 (gp130), was historically considered hepatoprotective; however, accumulating experimental evidence predominantly identifies endogenous IL-11 as an amplifier of liver injury and maladaptive repair. In hepatocytes, IL-11 promotes oxidative stress, mitochondrial dysfunction, and cell death while limiting effective regeneration. In hepatic stellate cells, it sustains myofibroblastic activation and extracellular matrix production, while crosstalk with hepatocytes, macrophages, and the matrix reinforces a fibroinflammatory niche. In hepatocellular carcinoma, experimental and associative clinical evidence implicates IL-11 in tumor growth, invasion, metastatic colonization, postoperative recurrence, stromal remodeling, and immune suppression. These findings have supported the development of therapeutic strategies targeting the IL-11/IL-11RA axis, with the potential to provide broad therapeutic benefits across a wide spectrum of liver diseases. This review summarizes IL-11 regulation and signaling in liver disease; discusses its roles in liver injury, fibrosis, and hepatocellular carcinoma; and evaluates the opportunities and challenges of IL-11-targeted therapy.

The establishment of endometrial receptivity is a fundamental prerequisite for successful embryo implantation and the maintenance of pregnancy. Decidualization, a critical process in the maturation of endometrial receptivity, is intimately linked to implantation success. The precise molecular regulation of both processes is essential for normal pregnancy outcomes. Within the endometrium, the activation of the transcription factor signal transducer and activator of transcription 3 (STAT3) exhibits strict temporal and spatial specificity. Its phosphorylation levels peak during the mid-secretory phase, aligning perfectly with the window of implantation, thereby establishing STAT3 as a primary indicator of endometrial receptivity. Activated by crucial cytokines-including leukemia inhibitory factor (LIF), interleukin (IL)-11, and epidermal growth factor (EGF)-STAT3 operates through the Janus kinase (JAK)/STAT signaling pathway. It regulates the functional maturation, adhesive capacity, and polarity remodeling of endometrial epithelial cells, creating an optimal environment for blastocyst attachment. Concurrently, STAT3 acts as a central regulator of decidualization by directly driving the proliferation and differentiation of endometrial stromal cells (ESCs) while maintaining the stability of the decidual microenvironment. Furthermore, STAT3 modulates the local immune milieu by orchestrating immune cell polarization and cytokine networks, providing essential immunological support. Conversely, dysregulation of the STAT3 signaling pathway leads to impaired endometrial receptivity and defective decidualization, contributing to adverse reproductive outcomes such as implantation failure and miscarriage. This review comprehensively highlights the pivotal regulatory functions of the STAT3 pathway in endometrial receptivity and decidualization, establishing a robust theoretical foundation for future basic research and targeted clinical strategies.

In this study, we demonstrate that during diabetic wound healing, interleukin-11 (IL-11) promotes the M1 polarization of macrophages, which subsequently triggers fibroblast senescence through the enhanced release of pro-inflammatory cytokines IL-1β and IL-6. Notably, Rhoifolin (Rho) effectively inhibits IL-11-induced M1 polarization, alleviates the secretion of IL-1β and IL-6, and concurrently promotes the release of choline, thereby mitigating fibroblast senescence. Based on these mechanistic findings, we constructed a targeted delivery system by loading Rho into mesoporous silica nanoparticles and coating them with macrophage membranes (M-Rho). The M-Rho were then incorporated into a poly(L-lysine)-grafted hyperbranched poly(amidoamine) (PLL-g-HPA) hydrogel to fabricate microneedles (Gel@M-Rho MN). This integrated system enables macrophage targeting, controlled drug release, favorable mechanical properties, and excellent biocompatibility. Moreover, the system exhibits potent reactive oxygen species (ROS)-scavenging activity and effectively inhibits the growth of Escherichia coli and Staphylococcus aureus. In vivo animal studies confirmed that Gel@M-Rho MN significantly promotes M2 macrophage polarization, suppresses fibroblast senescence, and accelerates wound closure, angiogenesis, and collagen deposition. Collectively, this strategy, which modulates macrophage-fibroblast crosstalk, offers a multi-mechanistic synergistic therapeutic approach for diabetic wounds, holding substantial potential for clinical translation.

Interleukin-11 (IL-11), a member of the glycoprotein-130 cytokine family, has been implicated in inflammation-associated malignancies, including pancreatic cancer, where both IL-11 and its receptors are frequently overexpressed; however, the transcriptional mechanisms that regulate IL-11 expression remain unclear. To investigate this mechanism, promoter reporter assays, electrophoretic mobility shift assays, EGR1 knockdown experiments, gene expression analyses and three-dimensional spheroid invasion assays were performed in pancreatic cancer cells. In the present study, early growth response 1 (EGR1) was identified as a key regulator of insulin-like growth factor 1 (IGF-1)-induced IL11 transcription. Promoter analyses revealed a conserved EGR1-binding sequence (EBS) within the proximal IL11 promoter that is essential for IGF-1-responsive transcriptional activation. Electrophoretic mobility shift assays demonstrated that EGR1 directly binds to this site. Functional silencing of EGR1 markedly attenuated IGF-1-induced IL-11 expression and reduced invasive behavior in a three-dimensional pancreatic cancer spheroid model. Collectively, these findings delineated an IGF-1/EGR1/IL-11 signaling axis linking growth factor-dependent transcriptional regulation to invasive phenotypes and highlighted a potential therapeutic target in pancreatic cancer.

Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant disorder caused by germline mutations in STK11, and is characterized by gastrointestinal hamartomatous polyps, the recurrent development of which significantly impacts patients' quality of life. While stromal cells have been implicated in PJS polyp formation, their specific characteristics remain unclear. Domènech-Moreno et al identify polyp-enriched crypt top fibroblasts (pCTFs) as the pathogenic fibroblast population and demonstrate that interleukin (IL)-11, a major secretory factor produced by these cells, serves as a critical mediator linking STK11 deficiency to epithelial proliferation. The study reveals that Stk11 loss triggers IL-11 expression, which in turn reinforces the pathogenic pCTF phenotype through autocrine signaling, forming a feedforward loop. Importantly, IL-11 neutralization significantly reduces polyp formation in a faithful mouse model, providing strong preclinical evidence for therapeutic translation. This work represents a significant advance in our understanding of PJS pathogenesis and establishes IL-11 as a promising therapeutic target. Future investigations into the effects of IL-11 neutralization on established polyps will further refine the translational potential of these findings for preventive intervention strategies. © 2026 The Pathological Society of Great Britain and Ireland.

Cardiovascular health depends critically on the integrity of the vascular extracellular matrix (ECM) and the behavior of vascular smooth muscle cells (VSMCs), both of which can be adversely affected in vascular diseases. This study quantitatively evaluates the therapeutic potential of conditioned medium (CM) derived from bone marrow (BM-MSCs) and adipose-derived stem cells (ADSCs) in an elastase-injured human aortic smooth muscle cell (HASMC) model. We systematically varied seeding densities (2000, 5000, and 10,000 cells/cm[2]) and serum conditions to optimize the SC-SMC secretome for vascular repair. Our results indicate that neither BM-SMC nor AD-SMC CM significantly enhanced lysyl oxidase (LOX) activity. In fact, serum-supplemented BM-SMC CM significantly suppressed LOX activity at seeding densities of 2000 cells/cm[2] (p = 0.0378) and 10,000 cells/cm[2] (p = 0.0080) compared to injured untreated controls. High-density AD-SMC CM (10,000 cells/cm[2]) also resulted in a significant decrease in elastin levels (p < 0.05). In addition, serum presence was critical for maintaining the reparative phenotype. Serum-free (SF) conditions for both cell sources led to widespread, statistically significant reductions (p < 0.0001) in key repair and inflammatory biomarkers, including PDGF-AA, Leptin, Lipocalin-2, Osteopontin, RBP4, MMP-1, and IL-6. IL-11 emerged as a primary discriminatory biomarker, showing significant differences between BM and AD treatments at high seeding densities, with both sources causing a significant decrease (p < 0.0001) compared to injured untreated controls. These findings demonstrate that seeding density and serum conditions are critical variables that quantitatively modulate the efficacy of SC-SMC-CM. The study highlights that BM-SMC-derived CM offers a more stable platform for elastin maintenance under serum-free conditions, providing a foundation for developing tailored, cell-free regenerative therapies for cardiovascular disease.

Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease with limited treatment options. LTI-03 promotes alveolar epithelial cell survival and reduces profibrotic protein expression in experimental models of IPF. In this Phase 1b, randomized, double-blind, placebo-controlled dose-escalation study, 24 participants with IPF were randomized 3:1 to inhaled LTI-03 5 mg/day (N = 9), LTI-03 10 mg/day (N = 9) or placebo (N = 6) for 14 days and included in all analyses (ClinicalTrials.gov: NCT05954988). The primary endpoint was the incidence of treatment-emergent adverse events (TEAEs). Exploratory analyses included pharmacokinetics and disease-related biomarkers. LTI-03 was well-tolerated, with no treatment-related discontinuations, no severe TEAEs, and no evidence of airway obstruction by spirometry and associated symptoms. In deep bronchial brushings, both LTI-03 doses significantly reduced interleukin-11 (p = 0.0406 at 5 mg/day; p = 0.044 at 10 mg/day) and thymic stromal lymphopoietin (p = 0.0256 at 5 mg/day; p = 0.0128 at 10 mg/day) versus placebo. The 10 mg/day dose suppressed collagen type 1 alpha chain 1 (p = 0.0248), CXC chemokine ligand 7 (p = 0.0248) and galectin-7 (p = 0.0332). Other measured biomarkers were not significantly changed. The favorable safety profile and reductions in disease-related biomarkers support further evaluation of inhaled LTI-03 for IPF. This study was fully funded by Rein Therapeutics, Inc.