Cellular & Molecular Immunology[JOURNAL]
Sun
200 papers
Immunotherapeutic efficacy of Th1 stimulatory epitopes derived from Leishmania donovani enolase and triose phosphatase isomerase in experimental visceral leishmaniasis.
Ratnapriya S, Yadav AK, Sahasrabuddhe AA … +1 more , Dube A
Mol Immunol · 2025 Jul · PMID 40347781 · Publisher ↗
Visceral leishmaniasis is a lethal systemic disease which cannot be controlled by drugs alone given asymptomatic reservoirs and must include alternatives to modulate immune responses of the endemic contacts. Our previous...
Visceral leishmaniasis is a lethal systemic disease which cannot be controlled by drugs alone given asymptomatic reservoirs and must include alternatives to modulate immune responses of the endemic contacts. Our previous studies have yielded potential immunomodulatory proteins by proteomic approach and their peptides showed significant immunomodulation and prophylactic efficacies. The current study has been intended to evaluate immunotherapeutic potential of the lead peptides (P10, P14 and P15) and their combinations with BCG as adjuvant. Results indicated P10 + 14 as well as P10 + P15 to be the most potential therapeutic peptides cocktails as both these combinations reduced parasite burden by > 65 % eliciting remarkable cellular response. High level of IFN-γ, TNF-α and IL-12 with decreased TGF-β expression suggested skewing of immune response towards Th1 type. These results were further supported by strong DTH and lymphoproliferative responses indicating therapeutic potential of the peptide combinations and possibilities in Kala-azar elimination program.
Anti-inflammatory properties of Pleione bulbocodioides extract through STING/ NF-κB pathway inhibition.
Yun J, Zhang Y, Zhang H … +4 more , Xiao F, Wang Y, Xu P, Qu L
Mol Immunol · 2025 Jul · PMID 40345080 · Publisher ↗
The members of Pleione (Orchidaceae) are popular worldwide for their ornamental appeal and medicinal properties. Pleione bulbocodioides, a CITES Appendix II-listed species, has been traditionally used in dermatological t...
The members of Pleione (Orchidaceae) are popular worldwide for their ornamental appeal and medicinal properties. Pleione bulbocodioides, a CITES Appendix II-listed species, has been traditionally used in dermatological therapies but remains pharmacologically understudied. In this study, the in vitro anti-inflammatory effects of extracts from artificially cultivated P. bulbocodioides were investigated. We found the P. bulbocodioides extract (PE) significantly suppressed TNF-α/IFN-γ-induced expression of IL-6, IL-1β, CCL5, CCL8, CXCL8, CXCL3, and TMEM173 (STING) genes in both HaCaT cells and NHEKs. Transcriptomic analysis and Western blotting confirmed the inhibitory effects on STING/NF-κB signaling pathway of PE. And phytochemical characterization identified militarine and batatasin III as principal bioactive constituents responsible for STING/NF-κB pathway inhibition by PE. PE also demonstrated comparable anti-inflammatory efficacy in LPS-induced RAW 264.7 macrophages and SLS-irritated 3D reconstructed human epidermis. Thus, these findings indicate the potential of PE as a natural anti-inflammatory therapeutic or skincare ingredient for dermatological applications.
Knockdown of RRBP1 regulates endoplasmic reticulum stress to mitigate malignant progression and suppress bortezomib resistance of multiple myeloma cells by inhibiting GRP78 expression.
Wang J, Jia H, Lv S … +2 more , Zhang X, Duan Y
Mol Immunol · 2025 Jul · PMID 40345079 · Publisher ↗
BACKGROUND: Ribosome binding protein 1 (RRBP1) was reported to play a regulatory role in certain cancers. It was related to poor prognosis and drug resistance in multiple myeloma (MM), but its mechanism has not been repo...
BACKGROUND: Ribosome binding protein 1 (RRBP1) was reported to play a regulatory role in certain cancers. It was related to poor prognosis and drug resistance in multiple myeloma (MM), but its mechanism has not been reported before. Hence, its effect and the specific mechanism on MM cells were explored. METHODS: The expression levels of RRBP1 and Glucose-regulated protein 78 (GRP78) in MM tissues were detected by immunohistochemical assay. The expression levels of mRNA and protein were analyzed by qRT-PCR and western blot, respectively. MM cell viability and proliferation were tested by CCK-8 assay. Flow cytometry was used to detect cell apoptosis. Transwell assay was carried out to explore cell migration and invasion. RESULTS: The expression levels of RRBP1 and GRP78 were upregulated in MM tissues and MM cells. Transfection of sh-RRBP1 weakened the proliferation, migration and invasion abilities of MM cells. Knockdown of RRBP1 dropped GRP78 expression and diminished endoplasmic reticulum stress in MM cells. Moreover, Tunicamycin-induced apoptosis of MM cells was enhanced by RRBP1 knockdown. Compared to the control group, inhibition of RRBP1 expression increased the drug sensitivity of bortezomib-resistant MM cells. In addition, overexpression of GRP78 partially repealed the effectiveness of sh-RRBP1 on MM cells. CONCLUSION: Our study elucidated the inhibitory effect of RRBP1 knockdown on MM cells, which suggested that RRBP1 might be a novel target for the therapy against MM.
Identification of pyroptosis-related gene S100A12 as a potential diagnostic biomarker for sepsis through bioinformatics analysis and machine learning.
Lin S, Yan J, He S … +1 more , Luo L
Mol Immunol · 2025 Jul · PMID 40318597 · Publisher ↗
Sepsis is a non-discriminatory inflammatory reaction that can result in a diverse array of organ dysfunctions, which can be fatal. Pyroptosis is a programmed mechanism of cell death that is distinguishable from apoptosis...
Sepsis is a non-discriminatory inflammatory reaction that can result in a diverse array of organ dysfunctions, which can be fatal. Pyroptosis is a programmed mechanism of cell death that is distinguishable from apoptosis and other forms of cellular demise. However, the role of pyroptosis in sepsis remains to be further explored. In this study, by employing a combination of the difference analysis, WGCNA, Friends' analysis, and machine learning, the central gene S100A12 was successfully identified. S100A12 demonstrated superb diagnostic capabilities in both the integrated and external validation datasets. Furthermore, significant disparities were observed in the levels of monocytes, eosinophils, and neutrophils between sepsis patients and the control group, as per the findings of immune infiltration analysis. The aforementioned immune infiltrating cells exhibited an increase in expression levels among patients diagnosed with sepsis and were found to be significantly and positively associated with S100A12 expression. The results of the single-cell analysis indicated a significant expression of S100A12 in both neutrophils and monocytes, which was in complete alignment with the outcomes of immune infiltration. In summary, the pyroptosis-related gene S100A12 represents a potential biomarker for the diagnosis and treatment of sepsis.
Paeoniflorin as a potential agent for urticaria treatment: Suppressing mast cell degranulation through HMGB1/TLR4/NF-κB signaling inhibition.
Wang X, Chen A, Pang Y … +6 more , Hou C, Wang Y, Liu E, Zhao Y, Guo J, Li M
Mol Immunol · 2025 Jul · PMID 40318596 · Publisher ↗
INTRODUCTION: Paeoniflorin (PF) has strong immunomodulatory effects and has been widely used in the treatment of many diseases, but its mechanism of action in urticaria is not clear. The aim of this experiment was to inv...
INTRODUCTION: Paeoniflorin (PF) has strong immunomodulatory effects and has been widely used in the treatment of many diseases, but its mechanism of action in urticaria is not clear. The aim of this experiment was to investigate the role and mechanism of paeoniflorin in improving mast cell degranulation in urticaria. METHODS: The mouse model of urticaria was replicated by ovalbumin+ aluminum hydroxide method, and the mast cell degranulation model was induced by anti-DNP IgE+ Dinitrophenyl- Bovine Serum Albumin (DNP-BSA), and the mice and cells were intervened by different doses of PF. The histopathological changes of the dorsal skin were observed using hematoxylin-eosin (HE) staining, the infiltration of mast cells was observed by Toluidine blue staining, the expression of mast cell tryptase (MCT) was examined by Immunohistochemical staining, the cell viability was detected by CCK8 assay, and Rhod-2/AM flow cytometry assay to determine calcium ion content, enzyme-linked immunosorbent assay (ELISA) detected mast cell degranulation-associated factors, and Western blot analyzed HMGB1/TLR4/NF-κB signaling factors. RESULTS: PF reduced the number of scratches in mice, ameliorated histopathological damage in dorsal skin, decreased mast cell degranulation rate, reduced the levels of Ca, MCT, β-HEX, HIS, MCP-1, TNF-α, and IL-13, and inhibited the expression of HMGB1, TLR4, MyD88, NF-κB p65 (Nucleus), and p-IκBα. Moreover, Rec-HMGB1 reversed the effect of PF. CONCLUSION: PF mitigates urticarial mast cell degranulation through the inhibition of the HMGB1/TLR4/NF-κB signaling pathway, suggesting its potential as a therapeutic agent for the treatment of urticaria.
Smart materials in pharmacological drug development: Neutrophils and its constituents for drug delivery and consequent antitumor effects.
Cai S, Wei X, Li Q … +2 more , Jiang Z, Li L
Mol Immunol · 2025 Jul · PMID 40318595 · Publisher ↗
Neutrophil-based drug delivery systems for targeted therapy of cancer have been studied widely in the recent past. Chemotactic cytokines including colony-stimulating factors (CSFs) recruit various immune cells including...
Neutrophil-based drug delivery systems for targeted therapy of cancer have been studied widely in the recent past. Chemotactic cytokines including colony-stimulating factors (CSFs) recruit various immune cells including the neutrophils to the tumor microenvironment (TME) leading to enhanced metastasis. These cytokines can be targeted effectively by immunotherapeutic agents such as checkpoint inhibitors and mAbs that can lead to systemic toxicity. To minimize the systemic adverse effects, camouflaged nanoparticles can be used significantly as alternative therapeutic agents. The neutrophil-interacting NPs and neutrophil membrane coated NPs have been exploited recently for their antitumor properties in vitro and pose limited systemic adverse effects in vivo. Neutrophil-derived exosomes derived from immune cells can efficiently escape immune-surveillance and pass through the blood-brain barrier. They possess several intrinsic properties in drug delivery as they are nano-sized, extremely biocompatible, non-immunogenic, biodegradable, stable and can carry targeting agents with limited toxicity and display antitumor properties. Also, neutrophil-based nanotherapy is dependent on factors such as neutrophil kinetics and the physicochemical properties of NPs such as size, shape, and surface chemistry. Therefore, neutrophil-based drug delivery for cancer therapy via the use of polymer nanoparticles is widely studied as their clinical appliance in nanomedicine is still at its infancy.
Tph cells are expanded in IgA vasculitis nephritis.
Jiang Q, Su Z, Zheng K
Mol Immunol · 2025 Jul · PMID 40315784 · Publisher ↗
Ectopic lymphoid structures (ELSs) contribute to maintaining the chronic inflammation process of IgA vasculitis nephritis (IgAVN) and are associated with a more severe disease course. PD-1CXCR5CD4 T peripheral helper (Tp...
Ectopic lymphoid structures (ELSs) contribute to maintaining the chronic inflammation process of IgA vasculitis nephritis (IgAVN) and are associated with a more severe disease course. PD-1CXCR5CD4 T peripheral helper (Tph) cells are recognized as the main CD4 T cells that contribute to B cell immune responses and antibody production in ELSs. However, the role of Tph cells in the pathogenesis of IgAVN is currently unknown. Here, we showed that the frequency of circulating Tph (cTph) cells was higher in IgAV patients compared to healthy controls, and higher among those with nephritis than those without nephritis. In addition, the frequency of cTph cells was positively correlated with 24-hour urine protein and urine red blood cell levels in IgAVN patients. cTph cells from IgAVN patients expressed high levels of activation makers and B cell helper markers, including ICOS, Tigit, IL-21, and CXCL13, and induced memory B cell differentiation in vitro in the presence of IL-21. Taken together, these results suggest that PD-1CXCR5CD4 cTph cells are involved in the pathogenesis of IgAVN by inducing B cell differentiation through IL-21, serving as a promising target for the treatment of IgAVN.
Dexmedetomidine improve lung inflammation by regulating autophagy and apoptosis of CD4+ T cell via AMPK/mTOR signaling.
Luo R, Wang Z, Xu F … +1 more , Xie K
Mol Immunol · 2025 Jul · PMID 40311186 · Publisher ↗
OBJECTIVES: To investigate the protective effect and potential mechanism of dexmedetomidine (Dex) in acute lung injury (ALI). MATERIALS AND METHODS: C57BL/6 mice and EL-4 cells were used for in vivo and in vitro studies,...
OBJECTIVES: To investigate the protective effect and potential mechanism of dexmedetomidine (Dex) in acute lung injury (ALI). MATERIALS AND METHODS: C57BL/6 mice and EL-4 cells were used for in vivo and in vitro studies, respectively. Cecal ligation and puncture (CLP) method was used to prepare an acute lung injury model. After dexmedetomidine intervention, tissue and cell samples were collected to evaluate and measure the severity of lung damage, the proportion of Treg cells, the expression of autophagy-related protein levels and AMPK/mTOR pathways. RESULTS: Dex reduced lung damage, and IL-17a, MPO positive cells in the lung, decreased the levels of pro-inflammatory cytokines, and restrain autophagy and apoptosis via the activation of the AMPK/mTOR pathway and increase of the proportion of Tregs. CONCLUSIONS: Dex can inhibit the levels of autophagy and apoptosis, increase the proportion of Treg cells, and reduce CLP induced acute lung injury through regulating AKMP/MTOR pathway.
Bro p 3, an nsLTP1: The first major allergen identified in Broussonetia papyrifera pollen.
Jiang Z, Yin X, Chen Z … +3 more , Liu S, Meng J, Xu A
Mol Immunol · 2025 Jun · PMID 40294488 · Publisher ↗
BACKGROUND: Broussonetia papyrifera pollen is an important cause of allergy worldwide, yet its key allergenic components remain unclear. This study aims to identify and characterize the major allergen of B.papyrifera pol...
BACKGROUND: Broussonetia papyrifera pollen is an important cause of allergy worldwide, yet its key allergenic components remain unclear. This study aims to identify and characterize the major allergen of B.papyrifera pollen. METHODS: Patients with allergic rhinitis (AR) symptoms in B.papyrifera pollen season and positive skin prick test (SPT) to B.papyrifera pollen extract were enrolled. Serum sIgE was measured by ImmunoCAP. The pollen crude extract was immunoblotted with patients' sera. The major allergen was purified and subjected to mass spectrometry analysis. The cDNA of the allergen was cloned from a pollen cDNA library. The antigenicity of recombinant allergen was measured by ELISA. Overlapping peptides spanning the allergen were synthesized. Type 2 T cell epitopes were screened using patients' PBMC by IL-4 ELISpot. Cross-reactivity of the allergen was evaluated. RESULTS: B. papyrifera-sIgE was confirmed in 194 of 201 patients by ImmunoCAP. Bro p 3 was identified as major allergen by immunoblot. We purified, cloned the cDNA of, and determined the full-protein sequence of Bro p 3, an nsLTP1 with an average mass of 10264 Da. Recombinant Bro p 3 (rBro p 3) exhibited identical antigenicity as natural Bro p 3, with sensitization rates of 74.53 % and 78.89 %, respectively. Peptides Pep 7-21, Pep 10-24 and Pep 13-27 stimulated IL-4 secretion by T cells from 8, 9 and 8 out of 11 patients. Bro p 3-sIgE sensitization was significantly correlated to elevated sIgE of B. papyrifera, Morus alba, Morus. rubra, and Humulus scandens. It was also associated with the concurrence of conjunctivitis and conjunctivitis plus asthma. No IgE binding was found to the other two B.papyrifera nsLTPs. Bro p 3 inhibited the IgE binding to M. alba and H. scandens pollen extracts. CONCLUSIONS: We demonstrated that Bro p 3 is the major allergen of B. papyrifera pollen and the first allergen from this species with its full sequence determined. The I-R peptides of Bro p 3 represent its immunodominant type 2 T cell epitopes. Bro p 3 sensitization is relevant to clinical phenotypes and the cross-reactivity between M. alba, H. scandens and B.papyrifera pollen.
Ex vivo pre-activation shifts the in vivo differentiation of adoptively transferred CD8 T cells in a melanoma model.
Lu J, Hu J, Zhao Z … +8 more , Zhai X, Chen C, Zheng X, Yang Y, Zheng Y, Ye L, Tian Q, Wang Y
Mol Immunol · 2025 Jun · PMID 40273814 · Publisher ↗
Adoptive transfer of TCR-specific CD8 T cells represents a powerful experimental platform for investigating tumor-specific CD8 T cell responses within the framework of anti-tumor immunity. Genetic modulation of these tra...
Adoptive transfer of TCR-specific CD8 T cells represents a powerful experimental platform for investigating tumor-specific CD8 T cell responses within the framework of anti-tumor immunity. Genetic modulation of these transferred cells provides a robust strategy to elucidate the intrinsic molecular mechanisms underlying T cell differentiation and functionality, thereby offering critical insights to optimize tumor-specific CD8 T cell antitumor immunity in cancer immunotherapy. A key aspect of this approach is the ex vivo activation of primary T cells, which raises important questions regarding the impact of pre-activation on subsequent T cell differentiation. In this study, we explored the differentiation trajectories of pre-activated CD8 T cells and performed a comprehensive characterization of their epigenetic and transcriptional profiles using a murine melanoma model. Our findings revealed that ex vivo pre-activation not only attenuates progression towards terminal exhaustion in the tumor-draining lymph nodes (TdLNs) but also enhances the stem-like characteristics of CD8 T cells within the tumor microenvironment (TME). Leveraging comprehensive ATAC-seq and RNA-seq analyses, we demonstrated that pre-activation modulates the epigenetic landscape and transcriptional profile of CD8 T cells, fostering effector-related differentiation in the TdLNs while promoting stemness-associated programming in the TME. These findings highlight the profound influence of ex vivo pre-activation on the differentiation pathways of tumor-specific CD8 T cells, underscoring the necessity of taking these experimental framework-induced discrepancies into consideration for more accurate data interpretation in relevant researches.
Anti-inflammatory and antioxidative effects of Perilla frutescens-derived extracellular vesicles: Insights from Zebrafish models.
Huang J, Chen L, Li W … +1 more , Chang CJ
Mol Immunol · 2025 Jun · PMID 40267772 · Publisher ↗
Plant-derived extracellular vesicles have recently been extracted and recognized as promising bioactive molecules, owing to their distinctive biological properties and inherent therapeutic activities. In this study, we i...
Plant-derived extracellular vesicles have recently been extracted and recognized as promising bioactive molecules, owing to their distinctive biological properties and inherent therapeutic activities. In this study, we investigated the physicochemical characteristics, bioactive properties, and therapeutic potential of Perilla frutescens-derived exosome-like nanoparticles (PELNs). Transmission electron microscopy (TEM) revealed that PELNs exhibited a cup-shaped morphology, with a lipid bilayer and a size distribution ranging from 40 to 200 nm (mean: 68.4 ± 13.0 nm). The cargoes in PELNs were analyzed through multi-omics and small RNA sequencing. In vivo studies on zebrafish demonstrated that PELNs are non-toxic at experimental concentrations. A reduction in neutrophil migration to injured fins evidenced the anti-inflammatory properties of PELNs. Furthermore, a meta-analysis of transcriptomic data identified hundreds of differentially expressed genes (DEGs) across 12 samples of three experimental groups. These DEGs were annotated into three categories following gene ontology (GO) enrichment analysis. Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that these DEGs were involved in immune-related pathways, including complement and coagulation cascades, systemic lupus erythematosus, PPAR signaling pathways, and antigen processing and presentation. Twelve selected DEGs were validated by quantitative real-time PCR (qRT-PCR), with particular confirmation of the mpx and lcp1 genes via in situ hybridization. Furthermore, PELNs demonstrated antioxidative effects by mitigating reactive oxygen species (ROS) levels, as evidenced by measurements of four oxidative stress (OS) indicators (i.e., SOD, CAT, GSH, and MDA) in zebrafish larvae subjected to HO-induced OS. In summary, PELNs exhibit substantial anti-inflammatory and antioxidant properties, underscoring their potential as therapeutic agents for treating various inflammatory diseases.
miR-23a-mediated TRF2 repression in CD4 T cells from PLWH.
Nguyen LNT, Zhao J, Pyburn JS … +10 more , Wang L, Schank M, Banik P, Hill AC, Wu XY, Zhang Y, Ning S, El Gazzar M, Moorman JP, Yao ZQ
Mol Immunol · 2025 Jun · PMID 40253806 · Full text
CD4 T cells in people living with HIV (PLWH) on antiretroviral therapy (ART) often exhibit an inflammaging phenotype, characterized by persistent inflammation, immune activation, exhaustion, senescence, and apoptosis. We...
CD4 T cells in people living with HIV (PLWH) on antiretroviral therapy (ART) often exhibit an inflammaging phenotype, characterized by persistent inflammation, immune activation, exhaustion, senescence, and apoptosis. We have previously demonstrated that inhibition of telomeric repeat factor 2 (TRF2) protein causes accelerated telomere erosion and premature CD4 T cell aging in PLWH. In this study, we further investigated how TRF2 protein is inhibited in CD4 T cells from PLWH, focusing on the miRNA-mediated mechanism. We found that miR-23a is significantly increased, whereas TRF2 protein is repressed, in CD4 T cells from PLWH compared to healthy subjects (HS). Bioinformatics analysis revealed that the TRF2 3'UTR is a potential target of miR-23a. Co-transfection of miR-23a with a luciferase construct containing TRF2 3'UTR into HEK293T cells revealed that miR-23a suppresses TRF2 protein translation. Notably, T cell receptor (TCR) activation in CD4 T cells from both PLWH and HS increased miR-23a and decreased TRF2 protein expression. Furthermore, increasing miR-23a in CD4 T cells from HS led to a decrease in TRF2 protein level and an increase in cellular apoptosis - a phenotype similar to what we observed in PLWH. Moreover, the knockdown of miR-23a in CD4 T cells from PLWH increased TRF2, but not TRF1, protein levels. These results suggest that miR-23a negatively regulates TRF2 protein expression in CD4 T cells; thus, targeting miR-23a may increase TRF2 protein level, and thereby protect telomere integrity and restore CD4 T cell functions in PLWH.
Steap3 is a key node in regulating the phagosome escape of Listeria monocytogenes.
Li Z, Shao Y, Liu X … +4 more , Wan X, Xiong P, Wang L, Yuan J
Mol Immunol · 2025 Jun · PMID 40252499 · Publisher ↗
Listeria monocytogenes, a foodborne pathogen, poses a significant threat to human health due to its high mortality rate and increasing antibiotic resistance. This study investigates the role of Steap3 in regulating the e...
Listeria monocytogenes, a foodborne pathogen, poses a significant threat to human health due to its high mortality rate and increasing antibiotic resistance. This study investigates the role of Steap3 in regulating the early phagosomal escape of Listeria monocytogenes. We found that Steap3 expression is downregulated in dendritic and intestinal epithelial cells following infection, and its deficiency exacerbates bacterial proliferation both in vitro and in vivo. Mechanistically, Steap3 interacts with Gm2a and Sting to inhibit Listeria monocytogenes infection. Our results highlight Steap3 as a key regulator in dendritic and intestinal epithelial cells' defense against Listeria monocytogenes infection, suggesting the Steap3-STING/Gm2a axis is a potential therapeutic target for listeriosis. This study provides valuable insights into the molecular mechanisms underlying Listeria monocytogenes pathogenesis and host immune response, offering new directions for developing anti-Listeria monocytogenes therapies.
Methotrexate loaded extracellular vesicles attenuate periodontitis by suppressing ACSL1 and promoting anti-inflammatory macrophage.
Liu Z, Yang J, Tan G … +6 more , Shi Y, Tao D, Wang W, Li B, Jin F, He X
Mol Immunol · 2025 Jun · PMID 40245705 · Publisher ↗
Macrophages are crucial immune cells in periodontal tissues, which play key roles in both the destruction and repair of associated with periodontitis. Targeted modulation of macrophage function has emerged as a potential...
Macrophages are crucial immune cells in periodontal tissues, which play key roles in both the destruction and repair of associated with periodontitis. Targeted modulation of macrophage function has emerged as a potentially effective approach to influence periodontitis progression. This study investigates the effects of methotrexate-loaded extracellular vesicles (MTX-EVs) on inflammatory macrophage polarization both in vivo and in vitro. In a murine periodontitis model, MTX-EVs inhibited alveolar bone resorption, suppressed pro-inflammatory macrophage activation, and promoted anti-inflammatory macrophages. Mechanistically, MTX-EVs reduced acyl-CoA synthetase-1 (ACSL1) expression, which was elevated during inflammation. Inhibition of ACSL1 with triacsin-C in macrophages suppressed the inflammatory phenotype through the promotion of the oxidative phosphorylation (OXPHOS). In contrast, MTX-EVs counteracted the effects of ACSL1 overexpression on macrophage polarization and metabolism. Our findings suggest that targeting ACSL1 via MTX-EVs represents a therapeutic strategy for modulating macrophage polarization and improving periodontitis treatment outcomes.
LncRNA XIST inhibits mitophagy and increases mitochondrial dysfunction by promoting BNIP3 promoter methylation to facilitate the progression of KBD.
Liu R, Xiao Y, Huang S … +10 more , Wu H, Dong J, Zeng S, Li Y, Ye J, Wu W, Wang M, Zhang S, Lin Z, Song H
Mol Immunol · 2025 Jun · PMID 40179650 · Publisher ↗
The primary mechanisms underlying cartilage destruction in Kashin-Beck disease (KBD) involve excessive chondrocyte death and extracellular matrix (ECM) degradation. While long non-coding RNA XIST (lncRNA XIST) has been i...
The primary mechanisms underlying cartilage destruction in Kashin-Beck disease (KBD) involve excessive chondrocyte death and extracellular matrix (ECM) degradation. While long non-coding RNA XIST (lncRNA XIST) has been implicated in promoting chondrocyte injury in osteoarthritis (OA), its role in KBD-related chondrocyte injury remains poorly understood. In this study, joint tissues were collected from four healthy and four KBD-affected children, as well as five healthy and five KBD-affected adults, to assess the expression of lncRNA XIST. The results revealed a significant upregulation of lncRNA XIST in the cartilage tissues of KBD patients. To model KBD-induced chondrocyte damage in vitro, hypertrophic ATDC5 cells were exposed to 10 ng/ml T-2 toxin for 24 hours, which resulted in increased lncRNA XIST expression. Silencing lncRNA XIST was found to mitigate T-2 toxin-induced ECM degradation and chondrocyte apoptosis by alleviating defects in mitochondrial autophagy and dysfunction. Mechanistically, lncRNA XIST promoted the methylation of the BNIP3 promoter by recruiting DNA methyltransferases (DNMTs) to the BNIP3 promoter region, thereby suppressing BNIP3-mediated mitophagy and exacerbating mitochondrial dysfunction. To establish a KBD rat model, rats were fed a low-selenium diet supplemented with T-2 toxin for four weeks. Knockdown of lncRNA XIST in these rats attenuated articular cartilage damage and apoptosis, while enhancing collagen II expression. In conclusion, lncRNA XIST accelerates KBD progression by inhibiting mitophagy and promoting mitochondrial dysfunction through increased BNIP3 promoter methylation.
NK cellular derived nanovesicles in tumor immunity.
Li D, Shi Y, Yu S … +7 more , Zhang B, Huang Z, Ling F, Mao X, Deng Y, Cai M, Luo W
Mol Immunol · 2025 Jun · PMID 40174421 · Publisher ↗
Natural Killer (NK) cells are a vital element of the innate immune system, and NK cell-based therapies have demonstrated efficacy against various malignancies. However, targeting solid tumors has been challenging due to...
Natural Killer (NK) cells are a vital element of the innate immune system, and NK cell-based therapies have demonstrated efficacy against various malignancies. However, targeting solid tumors has been challenging due to the low infiltration of NK cells into tumors and the effective evasion strategies employed by tumors. Recent studies have shown that NK cell derived nanovesicles (NK-NV) can not only replicate the functions of NK cells but also offer more advantages in clinical applications. They are capable of transporting various cellular components such as proteins, nucleic acids, and lipids across distances, thereby facilitating intercellular communication among various cells within the tumor microenvironment (TME). With the progress in nanomedical technology, these vesicles can be engineered to carry a range of functional elements and therapeutic agents to enhance their antitumoral capabilities. In this review, we summarize the current available literature on NK-NVs, discuss their potential biological functions and the role of non-coding RNAs (ncRNAs), and explore their application in the treatment of solid tumors.
MicroRNA-770 promotes polarization of macrophages and hemorrhoids by suppressing RYBP expression and monoubiquitination of histone H2A on Lys119 modification.
Zhou H, Liu T, Zhong S … +1 more , Yang W
Mol Immunol · 2025 Jun · PMID 40174420 · Publisher ↗
Hemorrhoid disease (HD) is a common proctological condition whose onset is associated with an abnormal inflammatory microenvironment; however, the underlying mechanisms remain unclear. In this study, pathological examina...
Hemorrhoid disease (HD) is a common proctological condition whose onset is associated with an abnormal inflammatory microenvironment; however, the underlying mechanisms remain unclear. In this study, pathological examination revealed a significant increase in MΦ1 macrophages in the hemorrhoidal tissue of patients with HD, along with elevated levels of inflammatory factors. qPCR results demonstrated that the expression of several members of the DLK1-DIO3 microRNA cluster, particularly miR-770, was significantly higher in the hemorrhoid tissue of patients with HD than in that of the control group. Luciferase reporter assays confirmed that RYBP is a target gene negatively regulated by miR-770. Additionally, qPCR and western blot analyses indicated that overexpression of miR-770 significantly downregulated the expression of PRC1 family genes and RYBP in THP-1 cells, while concurrently upregulating the expression of inflammatory factors such as NFKB, IL1b, IL4, TNF, and IFNG. The overexpression of miR-770 significantly induced the polarization of THP-1 cells toward MΦ1. Mechanistic studies using ChIP-seq revealed that miR-770 overexpression significantly reduced the number of gene promoters in MΦ1 cells that bind to histone H2AK119-Ub sites. Furthermore, the number of enriched DNA fragments from genes that bind to the + 1 transcription start site of histone H2AK119-Ub, such as NFKB1, IL1B, and TNF, was significantly lower than that observed in the control group. Therefore, we confirmed that miR-770, a genomic imprinted member of the DLK1-DIO3 region, negatively regulated the expression of the PRC1 family member RYBP, reduced the level of ubiquitination modification at histone H2AK119-Ub, and promoted the transcriptional activation of pro-inflammatory genes. This ultimately leads to MΦ1 polarization and the release of inflammatory factors, elucidating the epigenetic mechanisms underlying the occurrence of hemorrhoids.
Anti-tumor effectiveness of a novel bispecific antibody that blocks both PD-L1 and LAG-3.
Zhang C, Liu J, Sun M … +8 more , Gu T, Meng X, Zhu S, Zhang Y, Wang L, Chen Y, Zhang D, Wu Y
Mol Immunol · 2025 Jun · PMID 40168918 · Publisher ↗
Over the past few years, substantial progress with promising outcomes were achieved for the use of antibodies against programmed cell death protein 1 (PD-1) and its ligand (PD-L1) in immunotherapy. However, several issue...
Over the past few years, substantial progress with promising outcomes were achieved for the use of antibodies against programmed cell death protein 1 (PD-1) and its ligand (PD-L1) in immunotherapy. However, several issues still limit their effectiveness for anti-cancer therapy. Therefore, we designed a bispecific antibody (referred to as Ba-PL) against PD-L1 and T cell immune checkpoint lymphocyte activation gene-3 (LAG-3), in an attempt to block both targets to further improve immune efficacy against solid tumors. A bispecific T cell engager structure was used to connect the variable regions of the PD-L1 and LAG-3 antibodies in series. The antibody was prepared using a prokaryotic expression system, and its molecular and cellular-level affinity was assessed in vitro. Furthermore, we preliminarily evaluated its anti-tumor effects in mice. Collectively, the antibody prepared using the prokaryotic expression system had preferable tumor cell-targeting ability and blocked the interaction of PD-1 and LAG-3 with their ligands. Further, the results of the animal experiments demonstrated that the Ba-PL exerted a better anti-tumor effect in 4T1 and H22 tumor-bearing mice. Overall, our study suggests that this strategy has therapeutic potential for liver hepatocellular and breast invasive carcinoma.
Marvelon suppresses MC38 tumor growth and promotes anti-tumor immunity.
Kong F, Chen Y, Liu D … +4 more , Gao H, Yi Q, Zhang M, Li D
Mol Immunol · 2025 Jun · PMID 40158361 · Publisher ↗
Colorectal cancer is a prevalent and deadly malignancy globally, posing an important challenge due to its heterogeneity and treatment resistance. Although oral contraceptives have been shown to reduce the incidence of co...
Colorectal cancer is a prevalent and deadly malignancy globally, posing an important challenge due to its heterogeneity and treatment resistance. Although oral contraceptives have been shown to reduce the incidence of colorectal cancer, their impact on the anti-tumor effect of CD8 T cells remains unclear. Here we show that the contraceptive Marvelon plays an important role in anti-MC38 tumor immunity. The contraceptive Marvelon significantly inhibits MC38 tumor growth in vivo. Marvelon treatment promotes IFN-γ expression in CD8 tumor infiltrating lymphocytes, but shows dispensable impact on their exhausted profile. By further investigating the effects of Marvelon's primary components, Ethinylestradiol and Desogestrel, we reveal that Ethinylestradiol enhances IFN-γ production in Type 1 Cytotoxic T (Tc1) cells and significantly inhibits the viability of MC38 tumor cells, whereas Desogestrel exhibits minimal effects. This study not only redefines the role of oral contraceptives but also provides valuable insights for the development of novel immunotherapeutic strategies.
Brucella lipopolysaccharide deficiency with lipid A induces robust T cells immune response.
Zhang JD, Wang Q, Hu HX … +4 more , Guo KX, Guo CY, Chen HC, Liu ZF
Mol Immunol · 2025 Jun · PMID 40157278 · Publisher ↗
Brucella, an opportunistic intracellular parasitic bacterium, is classified as a Gram-negative organism. Lipopolysaccharide (LPS), as primary virulence factor of Brucella, includes lipid A, O-antigen, and core polysaccha...
Brucella, an opportunistic intracellular parasitic bacterium, is classified as a Gram-negative organism. Lipopolysaccharide (LPS), as primary virulence factor of Brucella, includes lipid A, O-antigen, and core polysaccharide, with lipid A being the principal component. The atypical structure of Brucella LPS, noted for its very-long-chain fatty acids, may suppress the host immune response, thus facilitating chronic disease development. The mechanism by which these chains induce immunosuppression remains poorly understood.This study aimed to investigate these chains through deletion of the BacA gene. We extracted LPS to stimulate Bone Marrow-Derived Dendritic Cells (BMDCs) in vitro and co-cultured them with T cells to induce proliferation and differentiation. The in vivo immune response to LPS was evaluated through routine blood tests, CD4 and CD8 assays, and lymphocyte stimulation indices. Our findings demonstrate that wild-type LPS from B. melitensis (Bm-WT) does not elicit an immunostimulatory response in vitro; rather, it promotes immune suppression in vivo. In contrast, LPS derived from B. melitensis with a mutated BacA gene (Bm-ΔBacA) disrupts the immune suppression and encourages the production of inflammatory factors. These findings underscore the crucial role of modifying lipid A through molecular biology techniques to advance bacterial vaccines and adjuvants.
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