Cellular & Molecular Immunology[JOURNAL]
Sun
200 papers
FBXW11 regulates macrophage polarization and enhances the anti-tumor activity.
Zhang S, Li R, Xie W … +6 more , Cui X, Li Y, Zhao H, Ren Q, Wang L, Zheng G
Mol Immunol · 2026 May · PMID 41934765 · Publisher ↗
Macrophages can be polarized to various states in physiologic and pathologic microenvironments. The simplified but widely accepted M1/M2 polarization states play contradictory roles in tumor progression. The ubiquitin-pr...
Macrophages can be polarized to various states in physiologic and pathologic microenvironments. The simplified but widely accepted M1/M2 polarization states play contradictory roles in tumor progression. The ubiquitin-proteasome system (UPS), particularly F-box proteins, has been reported to be involved in immune regulation. However, the role of F-box and WD-40 domain protein 11 (FBXW11) on macrophage remains unclear. Here, the effects of FBXW11 on macrophage polarization and anti-tumor function were investigated. The results showed that FBXW11 promoted macrophage proliferation and induced a mild M1 polarization phenotype in the absence of tumor cells. Furthermore, overexpression of Fbxw11 enhanced the M1 polarization of macrophages in tumor co-culture system. Moreover, overexpression of Fbxw11 also enhanced glucose uptake and increased mitochondrial reactive oxygen species (ROS) levels, while reducing the mitochondrial membrane potential (Δψ) in macrophages in tumor co-culture system. Functionally, Fbxw11 overexpression increased the phagocytosis and killing of A20 lymphoma cells. RNA-sequencing analysis revealed that FBXW11 activated critical innate immune pathways, including JAK-STAT, NF-κB, and Toll-like receptor signaling, and upregulated effector molecules such as IL-6 and type I interferons. Collectively, our results reveal that FBXW11 paly a positive role on macrophage M1 polarization and anti-tumor function, which broaden the knowledge about how UPS modulates innate immunity.
The association of systemic immune-inflammation index with Th17/Treg imbalance, disease severity (PASI), and quality of life (DLQI/PLSI) in patients with psoriasis vulgaris: A cross-sectional study.
Lin L, Li W, Gao X … +7 more , Li Q, Zhou X, Liu W, Zhong X, Yang Y, Zhang X, Luo Q
Mol Immunol · 2026 May · PMID 41932288 · Publisher ↗
OBJECTIVE: This cross-sectional observational study aimed to investigate the relationship between systemic immune-inflammation index (SII) and Th17/Treg cell imbalance in psoriasis vulgaris (PV) at a specific timepoint (...
OBJECTIVE: This cross-sectional observational study aimed to investigate the relationship between systemic immune-inflammation index (SII) and Th17/Treg cell imbalance in psoriasis vulgaris (PV) at a specific timepoint (upon admission), as well as its predictive value for disease severity. METHODS: A total of 112 PV patients and 112 healthy controls were enrolled. Blood cell counts were used to calculate SII. Levels of Th17/Treg cells, cytokines (IL-17, IL-22, IL-10, TGF-β1), disease severity (PASI), and related factors were analyzed. Patients were classified into mild (MPV) or moderate-to-severe (MSPV) groups, and logistic regression identified independent risk factors for severity. RESULTS: PV patients showed elevated neutrophils, SII, Th17, IL-17, and IL-22, but reduced lymphocytes, Treg, IL-10, and TGF-β1. SII positively correlated with PASI. MSPV patients had higher BMI, SII, Th17/Treg ratio, and cytokines (P < 0.05). BMI, SII, and Th17/Treg ratio were independent predictors of severity. CONCLUSION: This cross-sectional study indicates significant correlations of elevated SII levels in PV patients at a specific timepoint (upon admission) with Th17/Treg imbalance, disease severity (PASI), and poorer quality of life (DLQI/PLSI). These findings suggest the possibility of SII at a specific timepoint (upon admission) as a "snapshot" biomarker of the immuno-inflammatory status in PV.
CYR61 promotes obesity-induced kidney injury by activating endoplasmic reticulum stress.
Li B, Lv H, Gong K … +3 more , Gao Y, Zhen J, Hu Z
Mol Immunol · 2026 May · PMID 41855765 · Publisher ↗
The objective was to assess the influence of cellular communication network factor 1 (CYR61) in obesity-induced kidney damage, as well as its potential mechanisms. An obesity-induced kidney damage was established in rats...
The objective was to assess the influence of cellular communication network factor 1 (CYR61) in obesity-induced kidney damage, as well as its potential mechanisms. An obesity-induced kidney damage was established in rats using a high-fat diet (HFD), and human proximal tubule epithelial (HK-2) cells were treated with palmitic acid (PA) for an in vitro model. Biochemical analysis was performed using test kits. The influence of CYR61 on kidney damage were evaluated by HE staining, periodic acid-Schiff staining, Masson's trichrome staining and western blot. The effect of CYR61 on cell apoptosis in vitro was assessed employing flow cytometry. The influence of CYR61 on lipid accumulation in vitro was assessed by Oil red O staining. Besides, the protein and mRNA expression levels were determined via western blot, immunohistochemistry, immunofluorescence and qRT-PCR. CYR61 was upregulated in rats with HFD-induced kidney injury and PA-treated HK-2 cells. CYR61 knockdown ameliorated metabolic parameters, kidney injury, oxidative stress, apoptosis, and inflammation, while suppressing endoplasmic reticulum (ER) stress in rats with HFD-induced kidney damage. CYR61 knockdown inhibited apoptosis, inflammation, oxidative stress, lipid accumulation and ER stress in the PA-treated HK-2 cells; however, tunicamycin reversed these inhibitory effects. These findings confirmed that CYR61 knockdown could ameliorated oxidative stress and inflammation in PA-treated HK-2 cells and HFD-induced renal damage in rats by suppressing ER stress.
The role of macrophages in the immune microenvironment of splenic ectopic pregnancy.
Li L, Kang M, Chen S … +6 more , Lu X, Song Y, Li H, Wang T, Jia C, Xu C
Mol Immunol · 2026 May · PMID 41825266 · Publisher ↗
Splenic ectopic pregnancy is a rare and life-threatening condition, with no prior studies exploring its immune microenvironment. We analyzed immune cell alterations in splenic ectopic pregnancy and the potential role of...
Splenic ectopic pregnancy is a rare and life-threatening condition, with no prior studies exploring its immune microenvironment. We analyzed immune cell alterations in splenic ectopic pregnancy and the potential role of macrophages in pregnancy using immunohistochemical staining, transcriptomic profiling, and histological analysis. Our findings suggest that M2 macrophages may play a crucial role in maintaining successful pregnancy. The biological effects of macrophages on trophoblast cells were evaluated through CCK-8, migration, and invasion assays. Our results demonstrated that in splenic ectopic pregnancy tissues, significant reductions in CD20 B cells, CD8 T cells, and CD86 M1 macrophages were observed within splenic regions, while CD206 M2 macrophages were markedly increased in areas of trophoblast cell infiltration. This predominance of M2 macrophages may promote embryonic survival in splenic ectopic implantation. Transcriptomic and histological analyses of endometrial tissues from recurrent miscarriage (RM) patients revealed comparable M1/M2 macrophage dysregulation. In vitro experiments further demonstrated that M2 macrophages significantly enhanced trophoblast cell migration and invasion via PDGFR-β and PI3K-AKT-mTOR pathway. This study is the first to analyze the immune microenvironment of splenic ectopic pregnancy, revealing the critical role of M2 macrophages in maintaining normal immune tolerance.
FNDC4 modulates macrophage responses and suppresses NF-κB in sepsis-induced lung injury.
Chen J, Li J, Huang Y … +7 more , Fan Y, Li W, Ye J, Liu G, Jiang B, Pan S, Gao C
Mol Immunol · 2026 May · PMID 41819760 · Publisher ↗
Regulation of pulmonary macrophages and their related functions is crucial for preventing further deterioration in many diseases. Fibronectin III domain-containing 4 (FNDC4) is a secreted factor with high homology to the...
Regulation of pulmonary macrophages and their related functions is crucial for preventing further deterioration in many diseases. Fibronectin III domain-containing 4 (FNDC4) is a secreted factor with high homology to the exercise-related myokine irisin (FNDC5) and has been reported to be significantly upregulated in multiple mouse models of inflammation and under human inflammatory conditions. Here, we investigated the role and mechanisms of FNDC4 in regulating pulmonary macrophage function and the NF-κB pathway in sepsis. Plasma samples and clinical data from sepsis patients and healthy volunteers were collected to quantify FNDC4 levels and analyze their association with sepsis severity. In vivo, septic rat models with different disease severities were established to evaluate the effects of FNDC4 on lung injury. In vitro, LPS-stimulated mouse macrophages (RAW264.7) were preincubated with varying concentrations of FNDC4 to explore its functional effects and underlying mechanisms. Clinically, plasma FNDC4 levels were lower in sepsis patients than in healthy controls and were positively correlated with sepsis severity. In animal experiments, FNDC4 administration effectively alleviated sepsis-induced lung injury. In cell-based assays, FNDC4 preserved the proliferation and migration of LPS-stimulated RAW264.7 cells and reduced their apoptosis rate, while also inhibiting phosphorylation-dependent activation within the NF-κB pathway. Collectively, these findings suggest that FNDC4 may reflect sepsis severity and that exogenous FNDC4 can mitigate sepsis-related lung damage in vivo, potentially through modulation of the NF-κB signaling pathway, indicating its potential therapeutic value in sepsis.
m⁶A-modified circMELK regulates nasopharyngeal carcinoma progression via a YTHDF1/circMELK-miR-4775-HMGA2 feedback loop.
Yi Q, Zhong K, Chen Z … +4 more , Ouyang X, Zhu W, Liang L, Zhong J
Mol Immunol · 2026 May · PMID 41812494 · Publisher ↗
BACKGROUND: Circular RNAs (circRNAs) are emerging regulators in tumor biology. However, their roles in nasopharyngeal carcinoma (NPC) remain poorly defined. METHODS: By analyzing GSE190271, we identified hsa_circ_0138742...
BACKGROUND: Circular RNAs (circRNAs) are emerging regulators in tumor biology. However, their roles in nasopharyngeal carcinoma (NPC) remain poorly defined. METHODS: By analyzing GSE190271, we identified hsa_circ_0138742 (circMELK) as significantly upregulated in NPC. Functional assays in vitro and in vivo were performed to explore its biological role. Mechanistic studies included RIP, ChIP, RNA pull-down, dual-luciferase assays, and rescue experiments. RESULTS: circMELK was markedly elevated in NPC tissues and cells. Silencing circMELK inhibited NPC cell proliferation, migration, and invasion, while overexpression enhanced these malignant traits. Mechanistically, YTHDF1-mediated m6A modification serves as a key determinant for the cytoplasmic export of circMELK. There, circMELK acts as a ceRNA for miR-4775, relieving suppression of HMGA2. Elevated HMGA2 upregulates YTHDF1 by transcriptional activation, forming a YTHDF1/circMELK-miR-4775-HMGA2 positive feedback loop that drives epithelial-mesenchymal transition (EMT) and promotes metastasis. CONCLUSION: circMELK promotes NPC progression via a novel m6A-dependent ceRNA regulatory loop. Targeting this axis may offer new therapeutic opportunities.
Phillyrin attenuates TGF-β1-induced pulmonary fibrosis by modulating the Nrf2/HO-1 pathway and epithelial-mesenchymal transition.
Yu J, Liu Y, Song H … +11 more , Liu L, Li L, Luo Y, Ma Y, Zhu R, Liu X, Xia S, Zhang D, Meng J, Li W, Niu X
Mol Immunol · 2026 May · PMID 41812493 · Publisher ↗
BACKGROUND: Phillyrin (Phi), a natural lignan glycoside derived from Fructus Forsythiae, has been reported to exhibit anti-inflammatory and antioxidant activities. In this study, we investigated its therapeutic potential...
BACKGROUND: Phillyrin (Phi), a natural lignan glycoside derived from Fructus Forsythiae, has been reported to exhibit anti-inflammatory and antioxidant activities. In this study, we investigated its therapeutic potential in a TGF-β1-induced model of epithelial-mesenchymal transition (EMT) in A549 human alveolar epithelial cells. METHODS: The mechanisms of Phi were initially predicted using network pharmacology and molecular docking. Subsequently, A549 cells were stimulated with TGF-β1 and treated with Phi. Key assessments included cell viability, inflammatory and oxidative stress markers, EMT-related proteins (E-cadherin, α-SMA, vimentin), and fibrosis-associated molecules (collagen I, fibronectin, MMP-2). The activation of the Nrf2/HO-1 antioxidant pathway was also examined. RESULTS: Phi significantly attenuated TGF-β1-induced EMT and fibrotic responses in A549 cells. It not only suppressed inflammatory cytokine production and oxidative stress but also restored epithelial marker expression and reduced mesenchymal and fibrotic protein levels. Moreover, Phi upregulated the Nrf2/HO-1 signaling pathway, enhancing cellular antioxidant capacity. CONCLUSION: These findings suggest that Phi possesses potent anti-inflammatory, antioxidant, and anti-fibrotic properties, effectively inhibiting TGF-β1-driven EMT in alveolar epithelial cells. Phi may represent a promising therapeutic candidate for treating idiopathic pulmonary fibrosis and other fibrotic lung diseases.
Mechanistic study of swertiamarin in treating ulcerative colitis by regulating YAP-mediated Wnt and Notch pathways for intestinal stem cell repair.
Chen J, Peng H, Chen J … +2 more , Liu Y, Chen L
Mol Immunol · 2026 May · PMID 41806558 · Publisher ↗
BACKGROUND: Ulcerative colitis (UC) is a chronic immune-mediated inflammatory disease. In 2024, the American Gastroenterological Association updated its guidelines for UC patients, shifting the treatment goal from "clini...
BACKGROUND: Ulcerative colitis (UC) is a chronic immune-mediated inflammatory disease. In 2024, the American Gastroenterological Association updated its guidelines for UC patients, shifting the treatment goal from "clinical remission" to "mucosal healing" and "histological healing." This highlights the vital role of the interaction between intestinal stem cells (ISCs) and immune cells in maintaining and repairing intestinal tissue homeostasis. However, effective regulatory approaches targeting ISC-immune crosstalk are lacking in current clinical practice. The traditional Chinese medicine Qinjiao, which is widely used in clinical prescriptions for treating UC, contains many iridoid compounds, but whether they can promote tissue healing by regulating the ISC immune microenvironment remains to be clarified. METHODS: UHPLC-MS and an ISC injury organoid model were applied to identify and screen the four major iridoid compounds in Qinjiao. Then, the pharmacodynamic effects of swertiamarin (SW) on UC mice, the proliferation and differentiation of colonic ISCs, and the related status of Wnt, Notch, and Hippo-YAP signaling pathways were analyzed using RT-qPCR and other methods. Finally, the mechanism in organoids was verified using the YAP inhibitor Verteporfin. RESULTS: This study found that SW, a bioactive iridoid compound from Qinjiao, alleviated weight loss, mitigated colon atrophy, and reduced DAI scores in UC mice. SW also restored the proliferation and differentiation of ISCs. It mitigated immune-inflammatory responses and repaired the mucosal barrier by modulating YAP nuclear translocation to activate Wnt/β-catenin signaling and downregulate Notch signaling, enhancing ISC proliferation and differentiation. CONCLUSION: This study revealed that iridoid compounds, represented by SW, are the primary active components in Qinjiao for treating UC by restoring mucosal barrier integrity through enhanced ISC proliferation and differentiation.
vtRNA1-1/p62 regulates macrophages autophagy in ankylosing spondylitis.
Jiang M, Ni J, Yu X … +11 more , Zhao H, Lu X, Cheng L, Li Z, Wu H, Pan Z, Qu L, Gao M, Cai G, Wang M, Pan F
Mol Immunol · 2026 May · PMID 41795403 · Publisher ↗
This research aims to investigate the role and mechanisms of the vtRNA1-1/p62 molecular axis in the regulation of autophagy in AS, with the goal of identifying novel diagnostic and therapeutic targets for AS. Clinical sa...
This research aims to investigate the role and mechanisms of the vtRNA1-1/p62 molecular axis in the regulation of autophagy in AS, with the goal of identifying novel diagnostic and therapeutic targets for AS. Clinical sample analysis revealed that the transcription levels of vtRNA1-1 and p62 decreased in the peripheral blood mononuclear cells (PBMCs) of the AS group; conversely, the levels of canonical autophagy-related genes (ATG3, ATG5) and inflammatory factors (TNF-α) significantly increased. Correlation analysis revealed that vtRNA1-1 levels were positively associated with p62 but were inversely associated with ATG3, ATG5, and TNF-α. In vitro cell experiments demonstrated that vtRNA1-1 depletion reduced p62 expression while increasing ATG3, ATG5, and LC3B levels. Computational modeling further confirmed significant interactions between vtRNA1-1 and p62. Notably, vtRNA1-1 and p62 demonstrated unique diagnostic value for AS, with their combination showing even greater diagnostic significance. This study innovatively links noncoding RNA regulatory networks with autophagy homeostasis imbalance, revealing that vtRNA1-1 may regulate macrophage autophagy through p62, thereby participating in the molecular pathogenesis of AS.
Navigating the frontier of CAR-T cell resistance: From underlying mechanisms to innovative therapeutic solutions.
Lan F, Song J, Chen X … +1 more , Zhang Y
Mol Immunol · 2026 Apr · PMID 41791174 · Publisher ↗
Chimeric antigen receptor (CAR)-T cell therapy has achieved remarkable success in the treatment of relapsed or refractory hematological malignancies, particularly acute B-cell lymphoblastic leukemia (B-ALL), B-cell lymph...
Chimeric antigen receptor (CAR)-T cell therapy has achieved remarkable success in the treatment of relapsed or refractory hematological malignancies, particularly acute B-cell lymphoblastic leukemia (B-ALL), B-cell lymphoma (BCL), and multiple myeloma (MM). However, resistance in hematological malignancies and limited immune responses in solid tumors remain major challenges for CAR-T cell therapy. Tumor antigen loss or modulation, dysregulated apoptotic signaling, CAR-T cell-intrinsic dysfunction, and immunosuppressive components within the tumor microenvironment (TME) significantly compromise therapeutic outcomes. Therefore, understanding the mechanisms that mediate resistance to CAR-T cell therapy and exploring strategies to overcome therapeutic failure are crucial for optimizing clinical results. This review systematically elucidates the mechanisms underlying resistance to CAR-T cell therapy and discusses potential countermeasures, including dual-targeted approaches, innovative CAR engineering strategies, TME reprogramming, and combination immunotherapies.
High fat diet promotes asthma by inhibiting the differentiation of regulatory T cells via E3 ubiquitin ligase ITCH.
Tong L, Su L, He J … +4 more , Chen Y, Chen Z, Tang L, Wu X
Mol Immunol · 2026 Apr · PMID 41791173 · Publisher ↗
Obesity, a rising global health issue, has been linked to the exacerbation of asthma, increasing both the risk of onset and disease severity. High-fat diet (HFD) has been shown to influence immune responses and worsen as...
Obesity, a rising global health issue, has been linked to the exacerbation of asthma, increasing both the risk of onset and disease severity. High-fat diet (HFD) has been shown to influence immune responses and worsen asthma in murine models, although the exact mechanisms remain unclear. In our study, we found that HFD significantly reduced the population of regulatory T cells (Tregs) in the lungs and led to increased eosinophilic inflammation in asthma. HFD was linked to alterations in lipid metabolism, particularly through the activation of the lipogenic enzyme acetyl-CoA carboxylase (ACC1) and inhibition of fatty acid oxidation. Additionally, treatment with Etomoxir, a CPT-1a inhibitor, diminished Treg proportions and Foxp3 expression. We also revealed that the E3 ubiquitin ligase ITCH, which regulates Treg function, was downregulated at the protein level under HFD conditions, despite unchanged mRNA levels. Overall, our research findings highlight the impact of high-fat diets on Treg function and immune regulation, providing insights for potential therapeutic strategies targeting lipid metabolism in inflammatory diseases like asthma.
Gamma delta T cells promote intestinal fibrosis via an interleukin-17A-induced transforming growth factor-beta signaling pathway in fibroblasts.
Li Y, Chen M, Chen C … +6 more , Huang B, Liu F, Liang D, Sun D, He Z, Lan C
Mol Immunol · 2026 Apr · PMID 41762938 · Publisher ↗
BACKGROUND: Gamma delta T (γδ T) cells are a subpopulation of T cells enriched in the mucosa and epithelium. Intestinal fibrosis is a common complication of Crohn's disease (CD). This study investigates the role of γδ T...
BACKGROUND: Gamma delta T (γδ T) cells are a subpopulation of T cells enriched in the mucosa and epithelium. Intestinal fibrosis is a common complication of Crohn's disease (CD). This study investigates the role of γδ T cells and their mechanistic involvement in driving fibrotic progression in CD. METHODS: A mouse model of Crohn's disease-associated intestinal fibrosis was established by intrarectal administration of 2,4,6-trinitrobenzenesulfonic acid (TNBS) in 50% ethanol. Two separate intervention groups were treated with either an anti-interleukin-17A (anti-IL-17A) antibody or an anti-γδ T cell receptor (anti-γδ TCR) monoclonal antibody (clone GL3). Fibrosis was assessed via histology, enzyme-linked immunosorbent assay (ELISA), and Western blot. Additionally, γδ T cells and fibroblasts were isolated and subjected to Transwell co-culture. Their proliferation, apoptosis, and fibrosis markers were subsequently analyzed using the Cell Counting Kit-8 (CCK-8) assay, flow cytometry, ELISA, and Western blot, respectively. RESULTS: Compared to the control group, the model group mice showed weight loss, colon shortening, fibrosis, collagen deposition, and elevated IL-17, γδ T cells, and fibroblasts. Anti-IL-17A or GL3 antibody intervention attenuated fibrosis and reduced these factors. In vitro, model cells exhibited increased IL-17, alpha-smooth muscle actin (α-SMA), and collagen expression, which was further upregulated by Transwell co-culture. In vivo, the transforming growth factor-beta (TGF-β)/Smad pathway was activated with upregulated connective tissue growth factor (CTGF) in the model group, while antibody intervention inhibited this pathway. These findings are consistent with the in vitro results. CONCLUSION: γδ T cells play a significant role in promoting CD intestinal fibrosis, potentially through the secretion of IL-17, which activates fibroblasts and enhances the TGF-β/Smad signaling pathway. Consequently, targeting or depleting these cells represents a promising therapeutic strategy for CD-related intestinal fibrosis.
Hippo kinase NDR1 crosstalks with GSK3 and positively regulates type I interferon-mediated antiviral innate immunity.
Shi T, Jiang W, Li R … +4 more , Liu H, Shao S, An H, Ma X
Mol Immunol · 2026 Apr · PMID 41762937 · Publisher ↗
Type I interferons (IFN-Is) are central mediators of antiviral innate immunity, yet the molecular pathways that fine-tune their rapid induction remain incompletely defined. Here, we identified the Hippo pathway kinase ND...
Type I interferons (IFN-Is) are central mediators of antiviral innate immunity, yet the molecular pathways that fine-tune their rapid induction remain incompletely defined. Here, we identified the Hippo pathway kinase NDR1 as a key positive regulator of IFN-β-mediated antiviral responses. NDR1 forms a constitutive complex with GSK3 and selectively blocks its interaction with Akt, thereby preventing Akt-dependent inhibitory phosphorylation of GSK3 at Ser21/9 and maintaining GSK3 activity. Sustained GSK3 function enables efficient STAT1 activation, a central event required for both the initiation and amplification of IFN-β production. Consequently, loss of NDR1 disrupts this regulatory module, leading to reduced STAT1 phosphorylation, diminished IFN-β expression, and increased viral replication in macrophages. These mechanistic defects are mirrored in vivo, as NDR1-deficient mice exhibit impaired systemic IFN-β responses and markedly heightened susceptibility to viral infection. Together, our findings establish a previously unappreciated NDR1-GSK3-STAT1 signalling axis that integrates Hippo pathway components into antiviral innate immunity and reveal NDR1 as a potential target for enhancing host resistance to viral pathogens.
Adenovirus induces pediatric pneumonia via triggering macrophage polarization and IL-6 production via NF-κB activation.
Yuan X, Huang H, Fan H … +5 more , Xu X, Chen H, Lu B, Wang X, Lu G
Mol Immunol · 2026 Apr · PMID 41762478 · Publisher ↗
Human adenovirus (HAdV) is one of major pathogens that causes acute respiratory infections in children. Pulmonary macrophages mediated pulmonary immune response is crucial in both host defense against HAdV and lung patho...
Human adenovirus (HAdV) is one of major pathogens that causes acute respiratory infections in children. Pulmonary macrophages mediated pulmonary immune response is crucial in both host defense against HAdV and lung pathogenesis. However, the specific role of macrophage polarization in HAdV-induced lung injury remains unclear. Here, using bulk RNA-sequencing of bronchoalveolar lavage fluid (BALF) cells from children with HAdV pneumonia, we found that adenovirus infection upregulates the genes associated with macrophage polarization. Flow cytometry revealed a significantly higher proportion of M1 macrophages in severe cases compared to the non-severe cases. Mechanistically, in vitro infection of a human macrophage cell line demonstrated that HAdV directly induces M1 polarization and stimulates the production of inflammatory cytokine IL-6 via NF-κB activation. Our findings demonstrate that HAdV infection drives M1 macrophage polarization and IL-6 production through NF-κB signaling pathway, elucidating a key mechanism underlying the excessive inflammation and lung injury in severe HAdV infection.
OPTN knockout alleviates OVA-induced airway inflammation in a mouse model of asthma.
Zhang Y, Wang Z, Chen J … +1 more , Wan Y
Mol Immunol · 2026 Mar · PMID 41707470 · Publisher ↗
OBJECTIVE: Asthma is a common inflammatory disease of the respiratory system. This study aimed to investigate the effect of optineurin (OPTN) gene knockout on airway inflammation in an ovalbumin (OVA)-induced asthma mous...
OBJECTIVE: Asthma is a common inflammatory disease of the respiratory system. This study aimed to investigate the effect of optineurin (OPTN) gene knockout on airway inflammation in an ovalbumin (OVA)-induced asthma mouse model. METHODS: An OVA-induced chronic asthma model was established in 6-8-week-old C57BL/6 wild-type and OPTN knockout mice. Lung inflammation and goblet cell hyperplasia were respectively evaluated by hematoxylin and eosin (H&E) staining and periodic acid-Schiff (PAS) staining. Levels of epithelial-derived alarmins (IL-33, TSLP, and IL-25), Th2 cytokines (IL-4, IL-5, and IL-13), and serum immunoglobulin E (IgE) were measured by enzyme-linked immunosorbent assay (ELISA). To further assess autophagic flux, additional experimental groups treated with the lysosomal inhibitor chloroquine were included, and autophagy-related markers were examined by immunohistochemistry and Western blotting. RESULTS: Histological analyses demonstrated that OPTN deficiency markedly attenuated OVA-induced asthma-like airway inflammation, as evidenced by reduced inflammatory cell infiltration, basement membrane thickening, goblet cell hyperplasia, and mucus secretion. ELISA results showed that serum IgE levels, the concentrations of alarmins and inflammatory cytokines in bronchoalveolar lavage fluid were significantly decreased in the OPTN group compared with the wild-type group. Furthermore, immunohistochemical and Western blot analyses revealed altered expression of the autophagy-related markers LC3 and p62 in OPTN-deficient lungs. The chloroquine treatment experiment suggested that OPTN might be involved in the regulation of autophagy in the lungs, but the relevant difference did not reach statistical significance. CONCLUSION: OPTN knockout effectively alleviates asthma-like airway inflammation, and the underlying mechanism may be associated with the regulation of autophagy.
S1PR3 antagonism ameliorates endothelial dysfunction in septic acute kidney injury through the ROCK1-Drp1 signalling pathway.
Xu Z, Yan J, Luo G … +7 more , Fu Q, Wang H, Zhang J, Fang X, Zhang S, Cheng B, Fang X
Mol Immunol · 2026 Mar · PMID 41691873 · Publisher ↗
OBJECTIVE: Sphingosine-1-phosphate receptor 3 (S1PR3) is predominantly expressed in endothelial cells and plays important roles in inflammatory responses. However, its contribution to the pathogenesis of septic acute kid...
OBJECTIVE: Sphingosine-1-phosphate receptor 3 (S1PR3) is predominantly expressed in endothelial cells and plays important roles in inflammatory responses. However, its contribution to the pathogenesis of septic acute kidney injury (S-AKI) remains poorly defined. This study aimed to elucidate the role and underlying mechanisms of S1PR3 in endothelial dysfunction during S-AKI. METHODS: S-AKI was induced in mice by intraperitoneal lipopolysaccharide (LPS) injection. Renal endothelial function and mitochondrial integrity were assessed by flow cytometry, Evans blue dye (EBD) assays and transmission electron microscope (TEM). Mechanistic studies were conducted in human umbilical vein endothelial cells (HUVECs) using the S1PR3 antagonist TY-52156 and liposomal formulations. RESULTS: Serum creatinine (SCr), blood urea nitrogen (BUN) and renal S1PR3 expression were significantly increased 24 h after LPS challenge in wild-type mice, with S1PR3 predominantly localised to endothelial cells. Compared with S1pr3 mice, S1pr3 mice exhibited improved renal function, reduced leukocyte infiltration and enhanced ATP production. S1PR3 activation was associated with mitochondrial dysfunction, cytoskeletal remodelling and increased endothelial permeability. In vitro, TY-52156 reduced mitochondrial Ca accumulation, restored ATP levels and preserved cytoskeletal organisation and adherens junction integrity. To improve solubility and biocompatibility, TY-52156 was encapsulated into negatively or neutrally charged liposomes, of which LP-Neg-TY-52156 showed superior efficacy. In vivo, LP-Neg-TY-52156 alleviated endothelial leakage, mitochondrial injury and renal dysfunction in S-AKI. CONCLUSION: Endothelial S1PR3 is a key mediator of mitochondrial dysfunction and barrier disruption in S-AKI. Liposomal delivery of S1PR3 antagonists represents a promising therapeutic strategy for preserving endothelial integrity and attenuating septic renal injury.
Association of anti-inflammatory microglia interleukins with clinical and radiological parameters in patients with multiple sclerosis - a single-centre study in a Polish population.
Mado H, Stasiniewicz A, Nafalska N … +8 more , Stopyra M, Furgoł T, Jezierzański M, Kisielewska W, Kubicka-Bączyk K, Niedziela N, Sowa P, Adamczyk-Sowa M
Mol Immunol · 2026 Mar · PMID 41687557 · Publisher ↗
INTRODUCTION: Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system characterized by immune-mediated demyelination and neurodegeneration. Currently, the prevailing concept emphasizes au...
INTRODUCTION: Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system characterized by immune-mediated demyelination and neurodegeneration. Currently, the prevailing concept emphasizes autoimmune mechanisms, with recent studies highlighting a critical role of microglial cytokines. STUDY OBJECTIVE: To determine the association between the anti-inflammatory microglial cytokines (IL-10, IL-4, IL-13) and selected clinical and radiological parameters of MS patients. MATERIAL AND METHODS: The study included 96 MS patients undergoing immunomodulatory therapy and 73 healthy controls. Venous blood samples (10 ml) were obtained from all participants. RESULTS: Serum IL-10 levels were significantly lower in the MS group compared to the controls. IL-10 levels differed across Expanded Disability Status Scale (EDSS) scores, with the highest median concentration observed in patients with an EDSS score ≥ 4.0. A moderate negative correlation was identified between IL-13 and C-reactive protein (CRP) levels. No significant associations were observed between cytokine concentrations and recent clinical relapses. CONCLUSIONS: Higher IL-10 concentrations were associated with greater disability, suggesting its potential utility as a biomarker of MS progression, particularly in non-RRMS phenotypes. The negative correlation between IL-13 and CRP suggests the systemic anti-inflammatory effects of IL-13.
Unraveling immune evasion in the tumor microenvironment: Mechanisms, therapeutic strategies, and future directions in cancer immunotherapy.
Chandrasekar GH
Mol Immunol · 2026 Mar · PMID 41678952 · Publisher ↗
The immune evasion that is encouraged by the tumor microenvironment (TME) is a key factor in the failure of cancer immunotherapies. This review addresses how tumor cells avoid immune surveillance, which is critically dep...
The immune evasion that is encouraged by the tumor microenvironment (TME) is a key factor in the failure of cancer immunotherapies. This review addresses how tumor cells avoid immune surveillance, which is critically dependent on cellular and molecular events associated with immune checkpoint signaling, the capture of immune surveillance cells, metabolic restructuring, and physical and hypoxic barriers. We also discuss the latest therapeutic options, including immune checkpoint blockers, metabolic and angiogenic combination therapies, and Macrophage reprogramming of tumors. Nonetheless, such challenges as therapeutic resistance and patient heterogeneity are still significant challenges. In the future, individualized immunotherapy with the use of precision oncology tools that integrate multi-omics profiling, artificial intelligence, and manipulation of the gut microbiome a promising opportunity. A better understanding of the dynamic TME and the individualized immune landscape is the key to effective immunotherapy and the attainment of durable clinical responses to various types of cancers.
Dynamic immune yin-yang in chronic myeloproliferative neoplasms mechanisms, therapeutic implications, and future directions.
Zhang H, Xiong H, Guo X … +4 more , Ma Q, Wang Y, Li L, Zhang L
Mol Immunol · 2026 Mar · PMID 41666701 · Publisher ↗
Chronic myeloproliferative neoplasms (MPNs) are associated with dynamic and multifaceted changes in their immune microenvironment. Throughout disease progression, the interplay between pro-inflammatory ("yang") and immun...
Chronic myeloproliferative neoplasms (MPNs) are associated with dynamic and multifaceted changes in their immune microenvironment. Throughout disease progression, the interplay between pro-inflammatory ("yang") and immunosuppressive ("yin") cytokines and immune cells shapes the immune milieu and drives clinical progression. Sustained production of pro-inflammatory cytokines-such as interleukin-6 (IL-6) and interleukin-1β (IL-1β)-promotes clonal expansion and accelerates disease progression. Conversely, immunosuppressive mediators, including transforming growth factor-β (TGF-β) and interleukin-10 (IL-10), allow malignant clones to evade immune surveillance through the suppression of effector T-cell and natural killer (NK) cell cytotoxic functions. This dualistic immune state, with hyperactivation in early disease and immunosuppression in advanced stages, reflects the clinical and biological heterogeneity observed in MPNs. Emerging immunomodulatory therapies-such as interferon-α, Janus kinase (JAK) inhibitors, and other immunoregulatory agents-have demonstrated efficacy primarily by restoring immune balance. This review outlines the dual roles of immune cells and cytokines in MPN pathophysiology, emphasizes the significance of immune yin-yang imbalance, and evaluates current and prospective immunotherapeutic strategies for targeted immunologic intervention.
Sophora tonkinensis reprograms tumor-associated macrophages to M1-like phenotype and exerts anti-hepatocellular carcinoma effects.
Huang S, Wen J, Chen X … +10 more , Wang X, Guo Y, Liu L, He C, Lu Z, Huang A, Zhan X, Zhao J, Xiao X, Bai Z
Mol Immunol · 2026 Mar · PMID 41666700 · Publisher ↗
ETHNOPHARMACOLOGICAL RELEVANCE: Sophora tonkinensis radix et rhizoma is a medicinal herb traditionally used to treat inflammatory diseases and various types of cancer, previous phytochemistry studies have identified abun...
ETHNOPHARMACOLOGICAL RELEVANCE: Sophora tonkinensis radix et rhizoma is a medicinal herb traditionally used to treat inflammatory diseases and various types of cancer, previous phytochemistry studies have identified abundant alkaloids and flavonoids as the major bioactive components with anti-inflammatory, anti-tumor, hepatoprotective and immunomodulatory pharmacological effects, but their effects on Tumor-associated macrophages (TAMs) and the tumor immune microenvironment have not been systematically explored. AIM OF THE STUDY: This work aimed to establish whether a standardized extract of Sophora tonkinensis (STE) can halt IL-4-driven M2 macrophage polarization, reprogram established M2-like tumor-associated macrophages toward a pro-inflammatory M1-like phenotype, and clarify the underlying molecular mechanisms and in vivo efficacy of these immunomodulatory actions. MATERIALS AND METHODS: Bone-marrow-derived macrophages (BMDMs) were polarized to an M2 phenotype and subsequently treated with STE. Expression of the M1/M2 markers Arg-1, CD206, iNOS, and CD86 in these macrophages was quantified by immunoblotting, qPCR, and flow cytometry. The impact of STE-pretreated M2-conditioned medium on the proliferation, migration, and invasion of Hepa 1-6 cells was then examined. H22 cells were subcutaneously inoculated into Balb/c mice to assess STE's effects on the macrophage landscape within the tumor immune microenvironment and to evaluate its antitumor efficacy. RESULTS: STE dose-dependently suppressed IL-4-induced Arg-1 and CD206 while up-regulating iNOS and CD86, indicating a blockade of M2 polarization and a shift toward an M1 signature. Mechanistically, STE markedly increased JAK1 and STAT1 phosphorylation. Functionally, it potently inhibited invasion and migration of Hepa 1-6 cells. In tumor-bearing mice, robust suppression of tumor growth was accompanied by a pronounced reduction in M2-like TAMs and a reciprocal increase in M1-like macrophages within the tumor microenvironment. CONCLUSION: STE reprograms TAMs via the JAK1/STAT1 axis and exhibits robust antitumor activity, underscoring its promise as a natural, macrophage-targeted immunotherapeutic that warrants further investigation for integration into cancer treatment strategies.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe