Molecular Immunology[JOURNAL]
Sun
200 papers
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.
CYP1B1 as a therapeutic target for S. aureus-induced mammary gland inflammation.
Fu S, Zhao S, Fang Y … +6 more , Yang B, Yang C, Liu J, Wang H, Xu Y, Miao J
Mol Immunol · 2026 Mar · PMID 41691874 · Publisher ↗
Staphylococcus aureus (S. aureus) is a predominant zoonotic pathogen responsible for the most severe forms of mastitis, posing a major challenge to global dairy production and health of women. Its sophisticated pathogene...
Staphylococcus aureus (S. aureus) is a predominant zoonotic pathogen responsible for the most severe forms of mastitis, posing a major challenge to global dairy production and health of women. Its sophisticated pathogenesis renders it resistant to conventional therapies. In this study, we demonstrate that S. aureus infection triggers a concurrent upregulation of cytochrome P450 1B1 (CYP1B1) and vascular endothelial growth factor A (VEGFA), with CYP1B1 expression being regulated by the VEGFA-mediated signaling pathway. Furthermore, CYP1B1 exacerbates S. aureus-induced inflammatory damage and oxidative stress through estrogen metabolism. Notably, pharmacological inhibition of CYP1B1 significantly mitigates these detrimental effects. Our findings highlight the pivotal role of CYP1B1 in modulating the inflammatory response to S. aureus infection, identifying it as a promising therapeutic target for combating S. aureus-associated mastitis.
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.
Skin sensitisation to gluten in the absence and presence of atopic dermatitis drives changes in skin and systemic T cell phenotype composition in a rat model of food allergy.
Larsen JM, Benazzouz S, Törnblom VKW … +2 more , Bahl MI, Bøgh KL
Mol Immunol · 2026 Mar · PMID 41666699 · Publisher ↗
Atopic dermatitis is associated with higher risk for developing immune-related comorbidities, including other atopic diseases like food allergy as well as certain infections, autoimmune diseases, and cancers. It remains...
Atopic dermatitis is associated with higher risk for developing immune-related comorbidities, including other atopic diseases like food allergy as well as certain infections, autoimmune diseases, and cancers. It remains largely unknown whether this increased risk of comorbidities is attributable to underlying AD-induced changes in non-skin immune composition and function beyond the exacerbation of allergic immune responses. Here Brown Norway rats were sensitised to hydrolysed gluten though the skin in the absence or presence of AD-like skin inflammation induced by topical application of MC903. T cell phenotype composition was analysed in skin, blood, and gut tissues by flow cytometry. M1/M2 differentiation and cytokine production by intraperitoneal-derived macrophages stimulated with bacteria, inflammatory cytokines, or food allergens were analysed using flow cytometry and ELISA. Gut microbiota composition was analysed by partial 16S rRNA gene sequencing. Sensitisation in both the absence and presence of induced AD-like skin inflammation was found to predominantly affect T cell phenotype composition in skin and blood immune compartments. This systemic effect of AD had a minor effect on M1/M2 differentiation but did not affect cytokine production by intraperitoneal-derived macrophages. These findings highlight some systemic effects of skin sensitisation and AD that potentially could affect non-skin immune responses.
Mechanistic understanding of the protective effects of baicalein against the inflammatory response induced by Toxoplasma gondii in Ana-1 macrophages.
Wang X, Yu Z, Qi W … +6 more , Jiang Y, Yang P, Tu J, Fang Y, Zhou P, Zhang L
Mol Immunol · 2026 Mar · PMID 41666698 · Publisher ↗
Baicalein is an active flavonoid compound derived from Scutellaria baicalensis, a member of the Lamiaceae family, and has been widely reported to exhibit antioxidant, anti-inflammatory, and antimicrobial properties. Howe...
Baicalein is an active flavonoid compound derived from Scutellaria baicalensis, a member of the Lamiaceae family, and has been widely reported to exhibit antioxidant, anti-inflammatory, and antimicrobial properties. However, the precise mechanisms underlying the anti-inflammatory effects of baicalein in Toxoplasma gondii infection-induced inflammation remain unclear. This study aims to systematically investigate the regulatory effects of baicalein on inflammation associated with T. gondii infection and its molecular mechanisms. The results indicate that baicalein significantly inhibits T. gondii proliferation, the production of inflammatory mediators and reduces the expression levels of pro-inflammatory cytokines. Further experiments revealed that baicalein effectively blocks the excessive activation of the cGAS-STING and NOD-like receptor signaling pathways in T. gondii-stimulated Ana-1 cells, thereby inhibiting the amplification of inflammatory signals. Additionally, baicalein enhances the expression of autophagy-related proteins, promoting autophagy and alleviating oxidative stress-induced cellular damage and inflammation. In conclusion, this study demonstrates that baicalein exerts its anti-inflammatory effects by activating autophagy and inhibiting the excessive activation of cGAS-STING and NOD-like receptor signaling pathways, effectively suppressing T. gondii infection-induced macrophage inflammation. These findings provide new theoretical insights into the potential therapeutic application of baicalein in infectious diseases.
Characterizing two subtypes of osteosarcoma using G2M checkpoint-related genes and revealing its immune landscape.
Yang Z, Hong S
Mol Immunol · 2026 Mar · PMID 41650824 · Publisher ↗
BACKGROUND: Although the G2M checkpoint has been implicated in cancer metastasis in numerous studies, the genetic characteristics associated with the G2M checkpoint in Osteosarcoma (OS) remain unexplored. METHODS: Throug...
BACKGROUND: Although the G2M checkpoint has been implicated in cancer metastasis in numerous studies, the genetic characteristics associated with the G2M checkpoint in Osteosarcoma (OS) remain unexplored. METHODS: Through univariate Cox regression analysis, we screened for G2M checkpoint-related genes associated with OS survival. The ConsensusClusterPlus R package was employed for clustering analysis of the TARGET-OS dataset. Finally, the immune infiltration, biological function, mutation and drug sensitivity of different clusters were analyzed. Furthermore, the functional mechanism of KIF20B was elucidated through in vitro experiments. RESULTS: The TARGET-OS cohort was clustered into two distinct clusters (Cluster 1 and Cluster 2). Compared to Cluster 2, Cluster 1 showed a trend towards higher overall survival rates, with higher immune scores, stromal scores, and ESTIMATE scores, alongside lower tumor purity. Additionally, the infiltration levels of immune cells were substantially higher in Cluster 1. In vitro experiments confirmed that overexpression of KIF20B promoted the proliferation and invasion of SOSP-9607 cells and induced G2/M phase arrest, upregulating the expression of core proteins in the G2/M pathway. Overexpression of KIF20B enhanced the sensitivity of cells to zoledronic acid, while the G2/M pathway inhibitor AZD-1775 reversed this effect. CONCLUSION: This study elucidates the prognostic and immune microenvironmental characteristics of G2M checkpoint-related genes in OS, and validates the critical oncogenic function of KIF20B and its regulatory role in drug sensitivity. This study provides novel potential targets and strategies for molecular subtyping and targeted therapy of OS.
Luteolin alleviates ox-LDL-induced endothelial cell inflammation, apoptosis and ferroptosis by inhibiting the NAT10/ALOX12 pathway.
Yang B, Zhang H, Fang SJ … +2 more , Liu YZ, Zhang SY
Mol Immunol · 2026 Mar · PMID 41633065 · Publisher ↗
BACKGROUND: Luteolin has been shown to have inhibitory effects on many human diseases, including atherosclerosis (AS). However, the specific role and underlying molecular mechanisms of luteolin in the progression of AS n...
BACKGROUND: Luteolin has been shown to have inhibitory effects on many human diseases, including atherosclerosis (AS). However, the specific role and underlying molecular mechanisms of luteolin in the progression of AS need to be further elucidated. METHODS: Oxidized-low density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cells (HUVECs) was used to construct AS models in vitro. Cell proliferation, inflammation, apoptosis and angiogenesis were examined by CCK8 assay, EdU assay, ELISA, flow cytometry, and tube formation assay. The mRNA and protein levels of arachidonate 12-lipoxygenase (ALOX12) and N-acetyltransferase 10 (NAT10) were tested by qRT-PCR and western blot. The regulation of NAT10 on ALOX12 was confirmed by ac4C-RIP assay, RIP assay and dual-luciferase reporter assay. RESULTS: Luteolin promoted cell proliferation and angiogenesis, while inhibited ox-LDL-induced HUVECs inflammation, apoptosis and ferroptosis. Luteolin targeted ALOX12 to reduce its expression. ALOX12 overexpression reversed the inhibitory effect of luteolin on ox-LDL-induced HUVECs injury. NAT10 promoted the ac4C modification of ALOX12 to increase its expression. NAT10 knockdown alleviated ox-LDL-induced HUVECs injury by downregulating ALOX12, and the protective effect of luteolin against ox-LDL-induced HUVECs injury could also be reversed by NAT10 overexpression. CONCLUSION: Luteolin may inhibit ox-LDL-induced endothelial cell injury by suppressing NAT10-mediated the ac4C modification of ALOX12, thereby alleviating the progression of AS.
The dysregulation of B cells in systemic lupus erythematosus.
Wu X, Ma X, Zhang B … +4 more , Kang N, Liu YE, Shi X, Liu W
Mol Immunol · 2026 Feb · PMID 41619633 · Publisher ↗
B cells are pivotal components of the immune system, responsible for antibody production and immune regulation. Aberrant B cell activation is central to the pathogenesis of systemic lupus erythematosus (SLE), driven by d...
B cells are pivotal components of the immune system, responsible for antibody production and immune regulation. Aberrant B cell activation is central to the pathogenesis of systemic lupus erythematosus (SLE), driven by dysregulations of multiply signaling pathways, including B cell receptor (BCR), Toll-like receptor (TLR7/9), B cell-activating factor receptor (BAFF-R), and B-T cell interactions, along with related cytokines and interferons. These aberrant signaling pathways play diverse and integrated roles in SLE progression, contributing to autoantibody generation and tissue damage. This review examines the mechanisms linking aberrant B cell activation to SLE development, highlights recent genetic, epigenetic, and clinical insights, and discusses their implications for therapeutic management. Collectively, it provides a useful resource for researchers and clinicians in immunology and autoimmunity, enhancing the comprehension of B cell dysregulation in SLE.
Therapeutic applications of human umbilical cord-derived mesenchymal stem cell secretome in chronic inflammatory diseases and cancer: A recent update.
Nethaji K, Ashiq Shibili P, Dey A … +5 more , Nambidi S, Banerjee A, Barbon S, Pathak S, Duttaroy AK
Mol Immunol · 2026 Feb · PMID 41616420 · Publisher ↗
Chronic inflammatory disorders and cancer remain major global health challenges driven by persistent immune activation and tissue damage. The human umbilical cord-derived mesenchymal stem cell (hUC-MSC) secretome has eme...
Chronic inflammatory disorders and cancer remain major global health challenges driven by persistent immune activation and tissue damage. The human umbilical cord-derived mesenchymal stem cell (hUC-MSC) secretome has emerged as a promising cell-free therapeutic alternative owing to its potent anti-inflammatory, immunomodulatory, and regenerative properties. Comprising of cytokines, chemokines, growth factors, and extracellular vesicles enriched with bioactive miRNAs, the hUC-MSC secretome exerts its effects primarily through paracrine signaling. For this review, relevant literature was collected from established databases, including ScienceDirect, PubMed, and Google Scholar, using key terms such as "hUC-MSC secretome," "chronic inflammation," "exosomes," "tumor microenvironment," and "preconditioning." The search focused on studies published within the last five years, emphasizing in vitro and in vivo preclinical studies, original research, and review articles. Only studies specifically exploring hUC-MSC-derived secretomes were included, whereas those addressing cell-based therapies or secretomes from other MSC sources were excluded. Cumulative findings indicate that the hUC-MSC secretome alleviates chronic inflammation by releasing anti-inflammatory cytokines such as IL-10 and TGF-β, as well as regulatory miRNAs such as miR-29a-3p, miR-100-5p, and miR-125b-5p, which act via key signaling pathways including PI3K/AKT, Wnt/β-catenin, and JAK/STAT. These mechanisms collectively mediate anti-inflammatory responses, suppress epithelial-mesenchymal transition, enhance chemosensitivity, and promote tissue repair. This review aims to consolidate the emerging evidence that positions the hUC-MSC secretome as a next-generation cell-free therapeutic strategy for chronic inflammatory diseases, including major cancers, inflammatory bowel disease, rheumatoid arthritis, and neurodegenerative disorders, while highlighting current limitations and strategies to enhance the therapeutic efficacy and clinical applicability of the hUC-MSC secretome.
Toddalia asiatica (L.) Lam. induces apoptosis in rheumatoid arthritis fibroblast-like synoviocytes by modulating the PI3K/AKT/NF-κB pathway.
Niu J, Yan C, Zeng F … +4 more , Wang H, Fan Z, Chai Y, Liu C
Mol Immunol · 2026 Feb · PMID 41616419 · Publisher ↗
BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease. Although current pharmacological treatments can alleviate symptoms, they are often associated with significant adverse reactions and fail to halt disease pr...
BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease. Although current pharmacological treatments can alleviate symptoms, they are often associated with significant adverse reactions and fail to halt disease progression. Therefore, there is an urgent need to develop novel therapies derived from natural resources that have broad immunomodulatory effects with minimal side effects. The root of Toddalia asiatica (L.) Lam. (TA), a traditional remedy used by the Tujia and Miao ethnic groups for rheumatism, represents a promising natural candidate for RA treatment. However, its specific mechanism of action in RA is not fully elucidated. METHODS: Collagen-induced arthritis (CIA) rat models and interleukin-1β (IL-1β)-stimulated fibroblast-like synoviocyte (FLS) models were established to assess the therapeutic effects of TA on RA. Network pharmacology analysis was performed to identify potential therapeutic targets and associated pathways. Cellular functions were assessed through CCK-8, wound healing, and transwell migration assays. Apoptosis was evaluated using TUNEL staining and flow cytometry analysis. mRNA and protein expression levels were determined by qPCR, Western blotting, immunofluorescence, and immunohistochemical staining. RESULTS: TA alleviated joint swelling in CIA rats by reducing serum levels of pro-inflammatory cytokines and reactive oxygen species (ROS). It also modulated the Bax/Bcl-2 ratio and induced synovial cell apoptosis. Network pharmacology analysis revealed that common targets between TA and RA were enriched in the PI3K/AKT/NF-κB pathway. In vitro studies showed that TA inhibited the proliferation, migration, and invasion of MH7A cells, decreased the secretion of pro-inflammatory cytokines and ROS production, and promoted apoptosis. Mechanistically, TA suppressed the phosphorylation of key proteins in the PI3K-AKT and NF-κB pathways and reduced the nuclear translocation of NF-κB. CONCLUSIONS: TA exerts anti-RA effects by inhibiting the PI3K/AKT/NF-κB pathways and modulating the apoptosis balance of synovial fibroblasts. These findings provide a theoretical foundation for the clinical application of TA in RA treatment.
The activation of glial cells is involved in the pain and pruritus in allergic contact dermatitis.
Dai W, Zhang Z, Xu T … +7 more , Cai K, Luo A, Luo Z, Wang R, Lai Z, Wang J, Nie H
Mol Immunol · 2026 Feb · PMID 41579772 · Publisher ↗
BACKGROUND: The activation of glial cells in the central nervous system plays an important role in the neural signaling of chronic pain and pruritus. However, their involvement in the neural signaling of chronic pain and...
BACKGROUND: The activation of glial cells in the central nervous system plays an important role in the neural signaling of chronic pain and pruritus. However, their involvement in the neural signaling of chronic pain and pruritus in ACD remains to be investigated. To determine the effect of spinal glial cell activation in the coexistence of chronic pain and pruritus in the ACD model, we observed spinal glial cell activation in a mouse model of ACD induced by SADBE. METHODS: Square acid dibutyl ester (SADBE) was employed to establish ACD model mice and monitor the activation of spinal cord glial cells. Additionally, the Gene Expression Omnibus (GEO) database was utilized to analyze potential mechanisms. RESULTS: In the ACD model, the behaviors of licking and biting within 35 days after modeling were significantly increased. The expression levels of Iba-1, BDNF, LCN2, GRPR, and GFAP differed significantly from those of the control group. In addition, through GEO data analyses, a strong correlation has been found between pain and IFN-γ. Similarly, in vitro experiments revealed that IFN-γ increased the expression of Iba-1, CD16, and BDNF in BV2 cells and the release of LCN2 in primary astrocytes, thus activating spinal cord glial cells. IFN-γ also induced the phosphorylation of JAK1/STAT1 and the expression of IFNGR1 in BV2 cells and primary astrocytes. CONCLUSIONS: Collectively, the above findings suggest that the coexistence of chronic pain and pruritus in the ACD model is associated with the activation of spinal microglia and astrocytes. The underlying mechanism involves the binding of IFN-γ to its receptor IFNGR1, which is accompanied by the upregulation of JAK1/STAT1 signaling pathway phosphorylation.
Corrigendum to "Neferine reduces synovial inflammation and cardiac complications in a collagen-induced arthritis mouse model via inhibiting NF-κB/NLRP3 inflammasome axis" [Mol. Immunol. 182 (2025) 117-125].
Cao J, Zhang H, Ni Y … +1 more , Ning X
Mol Immunol · 2026 Feb · PMID 41579771 · Publisher ↗
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