Molecular Immunology[JOURNAL]
Sun
200 papers
Appropriate doses of ionizing radiation facilitate the proliferation and anti-tumor effects of γδ T cells through ERK and p38MAPK pathways in vitro.
Wang LL, Yang Y, Feng YB … +12 more , Zhao HQ, Hong Q, Chen FX, Chen L, Sun LQ, Lü XT, Sun F, Feng H, Chen K, Liu ZH, Guo LL, Zhou ZH
Mol Immunol · 2025 Dec · PMID 41218475 · Publisher ↗
Low dose ionizing radiation exhibits immunomodulatory properties. However, the impact of various doses of ionizing radiation on the antitumor responses of γδ T cells remains uncertain. The present study aimed to investig...
Low dose ionizing radiation exhibits immunomodulatory properties. However, the impact of various doses of ionizing radiation on the antitumor responses of γδ T cells remains uncertain. The present study aimed to investigate the effects of different doses of ionizing radiation on the proliferation, cytotoxicity and related molecular mechanisms of γδ T cells in vitro. Human γδ T cells were exposed to radiation by X-ray with different doses. CCK-8 assay was used to measure cell proliferation. Cytotoxic activity was detected using LDH release assay. Cytokines IFN-γ and TNF-α were measured by ELISA. Flow analysis was performed to determine the expressions of perforin, granzyme B and CD107a in/on γδ T cells. Protein expression of Bax, Bcl-2, p-ERK1/2, and p-p38MAPK in γδ T cells were evaluated by western blotting analysis. The results showed that γδ T cells of the 0.08 Gy dose group exhibited the most pronounced proliferation. The antitumor cytotoxicity of γδ T cells and the levels of IFN-γ and TNF-α in the 2 Gy and 4 Gy groups were higher than those in the control group. Accordingly, the expression of perforin, granzyme B, and CD107a in these two groups was upregulated significantly. Protein analysis indicated that in the 0.08 Gy group, the expression of Bcl-2 and p-ERK1/2 was significantly upregulated, whereas Bax was downregulated. In the 2.00 Gy group, the expression of p-p38MAPK was notably upregulated. These findings indicate that appropriate doses of ionizing radiation may promote γδ T cell proliferation through the ERK pathway, and enhance the cytotoxic activity of γδ T cells by upregulating critical cytokines production and the expression of cytotoxic molecules through the p38MAPK pathway.
Molecular pathways of radiation-induced lung damage: Effects of X-ray and Anti-PD-1 combination in a murine model.
Sun C, Zhang Y, Liu J … +8 more , Wei N, Li F, Fang Y, Li Y, Li S, Ma X, Wang Z, Wang X
Mol Immunol · 2025 Dec · PMID 41205481 · Publisher ↗
OBJECTIVE: To clarify the impact of X-ray irradiation combined with PD-1 immune checkpoint inhibitor treatment on lung tissue in a mouse model of radiation-induced lung injury (RILI) and to investigate its underlying mec...
OBJECTIVE: To clarify the impact of X-ray irradiation combined with PD-1 immune checkpoint inhibitor treatment on lung tissue in a mouse model of radiation-induced lung injury (RILI) and to investigate its underlying mechanisms. METHODS: A mouse RILI model was established by a single 16 Gy dose of whole-thorax irradiation. Mice were then treated with either an PD-1 inhibitor or a control. Lung injury and fibrosis were assessed by histological staining. Inflammatory cytokine levels (TNF-α, IL-6) were measured by ELISA. Macrophage M1 polarization was analyzed by flow cytometry and immunohistochemistry. The activation of the NF-κB signaling pathway was evaluated by Western blot. RESULTS: The lung injury indices in the group treated with irradiation combined with PD-1 inhibitor were higher than those in the irradiation-only group. Mechanistic studies found that PD-1 inhibitors promoted the activation of the NF-κB signaling pathway and simultaneously regulated macrophage polarization in lung tissue, promoting the differentiation of M1-type pro-inflammatory cells. CONCLUSION: Whole-thorax X-ray irradiation combined with PD-1 inhibitors can exacerbate lung injury and pulmonary fibrosis in mice, and the mechanism of action may be through the regulation of NF-κB signaling pathway activation to promote macrophage polarization towards the M1 type.
USP18 inhibits CVB3-induced pyroptosis and fibrosis of mouse cardiomyocytes through the IRF7/NF-κB signaling pathway.
Zhang Y, Yang L, Mu H … +4 more , Li N, Wang X, Lei H, Pang M
Mol Immunol · 2025 Dec · PMID 41205480 · Publisher ↗
The pathogenesis of viral myocarditis (VMC) is closely related to microbial infections, among which Coxsackievirus B3 (CVB3) is a common pathogenic microorganism. The aim of this study is to explore the potential mechani...
The pathogenesis of viral myocarditis (VMC) is closely related to microbial infections, among which Coxsackievirus B3 (CVB3) is a common pathogenic microorganism. The aim of this study is to explore the potential mechanism of USP18 in VMC caused by CVB3 infection. In this study, mice were injected intraperitoneally with 100 μL of CVB3 (10 TCID50) to construct a VMC mouse model, and HL-1 cells were exposed to CVB3 to establish a VMC cell model. The expression of related genes and proteins was detected using RTqPCR and Western blotting, and damage to cells and myocardial tissues was evaluated using ELISA, immunofluorescence, HE staining, etc. In this study, USP18 expression was upregulated in VMC- and CVB3-infected mice and HL-1 cells. USP18 knockdown not only promoted the expression of inflammatory factors (IL-18 and IL-1β), pyroptosis-related proteins (caspase-1, NLRP3, and GSDMD) and fibrosis-related proteins (α-SMA, Collagen I, and FN1) but also promoted the expression of myocardial injury markers (LDH, CK-MB, and cTnI) in vivo, aggravating the pathological damage to myocardial tissues. Moreover, USP18 overexpression inhibited CVB3-induced pyroptosis and fibrosis. Mechanistically, USP18 stabilizes IRF7 expression through deubiquitination, thereby promoting the binding of IRF7 to NF-κB, inhibiting the nuclear translocation of NF-κB, and ultimately inhibiting CVB3-induced pyroptosis and fibrosis and improving VMC. Our study suggests that upregulating USP18 expression may represent a new target for VMC treatment.
Plasma secretory protein genes in hepatocellular carcinoma and heart failure: Comorbidity and biological function exploration.
Cao L, Wang X, Ning Z … +8 more , Xie F, Li X, Chen Y, Geng Q, Liu J, Zhu Q, Ma L, Li Y
Mol Immunol · 2025 Dec · PMID 41192015 · Publisher ↗
BACKGROUND: This research aimed to elucidate the roles of plasma secretory protein genes in mediating the comorbid effects between hepatocellular carcinoma (HCC) and heart failure (HF). METHODS: A comprehensive analysis...
BACKGROUND: This research aimed to elucidate the roles of plasma secretory protein genes in mediating the comorbid effects between hepatocellular carcinoma (HCC) and heart failure (HF). METHODS: A comprehensive analysis utilizing Weighted Gene Co-expression Network Analysis (WGCNA), differential expression analysis, and advanced deep learning techniques was conducted to identify three plasma-secreted protein genes (Ficolin-3: FCN3, Fibroblast Activation Protein: FAP, High Mobility Group Box 2: HMGB2) as key players in the comorbid interplay between HCC and HF. RESULTS: Validation experiments confirmed the significant biological functions of these genes in disease pathogenesis. Additionally, dexamethasone and catechins were identified as promising candidates for pharmacological intervention in the prevention of HCC and HF. CONCLUSION: These findings unveil potential mechanistic pathways of comorbidity between HCC and HF, providing novel biological markers and therapeutic targets for the prognostic evaluation and treatment of these conditions, with substantial implications for refining clinical diagnosis and therapeutic strategies.
Role of the urokinase-type plasminogen activator system in viral infection and replication.
Yang S, Chen J, Shi X … +4 more , Wang J, Li L, Du S, Li C
Mol Immunol · 2025 Dec · PMID 41176919 · Publisher ↗
The urokinase-type plasminogen activator system (uPAs) consists of the urokinase-type plasminogen activator (uPA), its receptor (uPA receptor, uPAR) and the plasminogen activator inhibitor (PAI). Recent studies have reve...
The urokinase-type plasminogen activator system (uPAs) consists of the urokinase-type plasminogen activator (uPA), its receptor (uPA receptor, uPAR) and the plasminogen activator inhibitor (PAI). Recent studies have revealed that, beyond its well-established roles in promoting fibrinolysis and degrading extracellular matrix (ECM) proteins-thereby regulating tissue repair and tumor metastasis-this system also plays a significant role in viral infections. Specifically, the uPAs modulates viral infection processes by regulating the expression and activity of uPA and uPAR, which are involved in inflammatory response modulation, immune cell migration, and the infiltration of inflammatory cells during tissue repair in the context of viral infections. In this review, we summarize the roles of uPAs in various viral infections, aiming to deepen our understanding of the contributions of each uPA component and provide insights into potential strategies for inhibiting viral infection processes.
Neohesperidin ameliorates airway remodeling through suppressed airway inflammation and oxidative stress in ovalbumin-sensitized mice.
Cheng SC, Liou CJ, Chen YL … +3 more , Fang LW, Huang TH, Huang WC
Mol Immunol · 2025 Dec · PMID 41172705 · Publisher ↗
Neohesperidin, a natural flavonoid found in citrus plants, has been reported to exhibit anti-inflammatory and antioxidant activities. In this study, we investigated its therapeutic potential in an ovalbumin (OVA)-induced...
Neohesperidin, a natural flavonoid found in citrus plants, has been reported to exhibit anti-inflammatory and antioxidant activities. In this study, we investigated its therapeutic potential in an ovalbumin (OVA)-induced murine model of allergic asthma. Female BALB/c mice were sensitized and challenged with OVA, followed by intraperitoneal administration of neohesperidin at doses of 10 or 20 mg/kg. The primary assessments included airway hyperresponsiveness (AHR), inflammatory cell counts in bronchoalveolar lavage fluid (BALF), lung histopathology, immunohistochemical analysis, and evaluation of oxidative stress biomarkers. In parallel, BEAS-2B human bronchial epithelial cells were stimulated with IL-4 and TNF-α to assess the anti-inflammatory and antioxidant effects of neohesperidin in vitro. Neohesperidin significantly attenuated several pathological features of asthma, including AHR, inflammatory cell infiltration, goblet cell hyperplasia, and collagen deposition. It not only suppressed Th2 cytokine levels and pro-inflammatory mediators in BALF, but also enhanced the activity of antioxidant enzymes in the lungs. Moreover, neohesperidin downregulated COX-2 expression and upregulated HO-1 in lung tissues. In BEAS-2B cells, it inhibited the release of inflammatory cytokines, reduced reactive oxygen species production, and decreased monocyte adhesion. Taken together, these findings suggest that neohesperidin possesses immunomodulatory and antioxidant properties that contribute to the attenuation of airway inflammation and remodeling in allergic asthma. These results indicate that neohesperidin is a promising natural compound with therapeutic potential for asthma treatment.
ZBTB16 promotes the transcription of glycolytic enzyme PFKFB2 to participate in fibrogenesis in septic lung injury.
Tai Z, Wang C
Mol Immunol · 2025 Dec · PMID 41166797 · Publisher ↗
BACKGROUND: Sepsis is a severe systemic inflammatory response syndrome that leads to acute lung injury (ALI), which subsequently progresses to lung fibrosis. This study aims to investigate the role of zinc finger and BTB...
BACKGROUND: Sepsis is a severe systemic inflammatory response syndrome that leads to acute lung injury (ALI), which subsequently progresses to lung fibrosis. This study aims to investigate the role of zinc finger and BTB domain containing 16 (ZBTB16), a transcription factor, in septic lung injury. METHODS: The expression of Zbtb16 in the injured lung was evaluated using single-cell sequencing. The signaling pathways that can be regulated by Zbtb16 were predicted using gene set enrichment analysis (GSEA). Then, the functions of ZBTB16 and its potential molecular mechanism in fibrogenesis were explored in lipopolysaccharide (LPS)-induced ALI mice in vivo and LPS-induced MRC-5 cells and primary fibroblasts in vitro. RESULTS: Single-cell analysis showed that Zbtb16 was overexpressed in the fibroblasts of the injured lung. GSEA found that Zbtb16 might activate inflammatory response and glycolysis during lung injury. Silencing of Zbtb16 relieved lung injury, decreased lung wet/dry weight and myeloperoxidase (MPO) activity, reduced the levels of lactate dehydrogenase (LDH), total protein, and neutrophil in the BALF, and inhibited fibrogenesis in septic ALI mice. In LPS-induced fibroblasts, silencing of ZBTB16 suppressed the expression of inflammatory and fibrotic markers by inhibition of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 (PFKFB2)-mediated glycolysis. CONCLUSION: ZBTB16 promotes the transcription of glycolytic enzyme PFKFB2 to participate in fibrogenesis in septic lung injury. Our study may offer a potentially promising target for the treatment of fibrogenesis in septic lung injury.
Characterization of the lambda light chain repertoire and non-coding regions of equine immunoglobulins using the EquCab3 genome.
da Silva GM, Navas C, Carvalho MB … +8 more , Sampaio Y, Rocha MN, Gomes-Silva A, de Matos Guedes HL, Cunha L, Castilho LR, da Silva JL, Felicori LF
Mol Immunol · 2025 Dec · PMID 41166796 · Publisher ↗
Horse immunoglobulins have been utilized for over a century in serotherapy to treat venomous animal bites and various other conditions. However, molecular-level information about these immunoglobulins remains limited, pa...
Horse immunoglobulins have been utilized for over a century in serotherapy to treat venomous animal bites and various other conditions. However, molecular-level information about these immunoglobulins remains limited, particularly regarding immunoglobulin lambda light chains (Igλ), which constitute over 90 % of circulating antibodies. Despite the sequencing of the equine genome, the International ImMunoGeneTics information system (IMGT) has not yet annotated Igλ in its database, restricting the analysis of the horse antibody repertoire. In this study, we analyzed the equine Igλ repertoire and inferred the characteristics of the promoter regions and nearby co-stimulatory elements based on conserved human sequences. We find that some motifs from the promoter region of horse immunoglobulins showed a high rate of conservation between human and equine sequences, as an example of the octamer region. By mapping the V and J gene segment positions from EquCab2 to their corresponding positions in EquCab3, we constructed a library with new potential alleles. This impacted the annotation, since we identified the J gene segment J4S1, which shares the same sequence as the J5 and J6S1 gene segments, account for over 50 % of the annotated J genes. Our analysis, which included a 2-fold increase in the number of clones compared to previous studies, revealed a restricted use of V gene segments, with approximately 70 % of the repertoire derived from just four gene segments within subgroup 8. This preference can be attributed to the presence of several co-stimulatory elements near the promoter region. Additionally, our analysis indicated that the CDR-L3 region predominantly displays lengths of 10-11 amino acids, with serine (Ser) being the most common amino acid. Beyond enhancing the annotation and characterization of the equine Igλ repertoire, this study also identified non-coding regions, particularly promoter regions containing a conserved octamer and a TATA-Box, and their co-stimulatory elements, such as pyrimidine-rich region, and E-box. The findings of this research contribute to a better understanding of equine Igλ composition, gene usage, and promoter characteristics, ultimately advancing future studies involving the use of equine antibodies.
Small-molecule perturbation profiling reveals a mechanistic link between STING signaling and lipid metabolism in macrophages and dendritic cells.
Gmyrek L, Zhang J, Andrade M … +3 more , Hillette KR, Wu X, Park JM
Mol Immunol · 2025 Nov · PMID 41109016 · Publisher ↗
The DNA sensor cGAS and the signaling adaptor STING play a key role in the innate immune response to microbial and endogenous DNA in the cytoplasm. The cGAS-STING signaling pathway has evolved to promote immune defense a...
The DNA sensor cGAS and the signaling adaptor STING play a key role in the innate immune response to microbial and endogenous DNA in the cytoplasm. The cGAS-STING signaling pathway has evolved to promote immune defense and organismal fitness, yet its dysregulation can lead to chronic inflammation, autoimmunity, and neurodegeneration. Upon sensing double-stranded DNA, cGAS produces a cyclic dinucleotide second messenger that binds to STING in the endoplasmic reticulum. Ligand-bound STING translocates to the Golgi and activates a signaling cascade that results in interferon (IFN) gene transcription. These molecular events are mechanistically linked to intracellular lipid membrane dynamics and protein lipidation. To explore whether STING signaling is controlled by the availability and metabolic flux of cellular lipids, we screened small-molecule compounds targeting lipid metabolic pathways for their influence on STING agonist-responsive IFN induction. These screens identified inhibitors of the fatty acid synthase FAS and lipases as potent suppressors of STING signaling. An inhibitor of the cholesterol-esterifying enzyme SOAT1 enhanced STING-dependent IFN induction in mouse cells while attenuating it in human cells. From an analysis of STING sequences, we detected a difference in their lipid binding motifs that likely accounted for the species-specific effects of SOAT1 inhibition. Our findings reveal a connection between STING signaling and lipid metabolism and opportunities for expanding the toolbox for treating clinical conditions that arise from aberrant STING activity.
Corrigendum to "Regulation of macrophage pyroptosis by SIRT1 during Pseudomonas aeruginosa-induced pneumonia" (Mol. Immunol. 185 (2025) 7110).
Ding H, Xiao X, Zhan Y … +3 more , Lin Y, Xu C, Zeng Y
Mol Immunol · 2025 Nov · PMID 41106289 · Publisher ↗
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AMPK upregulates SOCS1 to promote TFEB nuclear transfer, enhances autophagy, inhibits macrophage M1 polarization and relieves acute lung injury.
Nie W, Gong C, Liu Y … +4 more , Yang J, Dai Q, Liao Y, Li F
Mol Immunol · 2025 Nov · PMID 41101172 · Publisher ↗
BACKGROUND: Acute lung injury (ALI) is a life-threatening inflammatory disease. Macrophage polarization plays a key role in the occurrence of pulmonary inflammation. Therefore, regulating the phenotype of macrophages is...
BACKGROUND: Acute lung injury (ALI) is a life-threatening inflammatory disease. Macrophage polarization plays a key role in the occurrence of pulmonary inflammation. Therefore, regulating the phenotype of macrophages is a potentially effective method for the treatment of ALI. This study aims to explore the potential molecular mechanism of SOCS1 in M1 polarization of macrophages and ALI. METHODS: The ALI animal model was established by intratracheal infusion of LPS (5 mg/kg), and the cell model was established by stimulating RAW264.7 macrophages with LPS (1 μg/mL). The levels of autophagy and macrophage markers were detected by immunofluorescence, MDC staining, western blot. ELISA was used to measure the levels of inflammatory cytokines. The level of MPO in the lungs was determined, and inflammatory cells and proteins in BALF were detected. RESULTS: The expressions of SOCS1, TFEB and p-AMPK decreased in the ALI model. Overexpression of SOCS1 inhibited the M1 polarization of macrophages induced by LPS, reduced the expressions of pro-inflammatory factors IL-1β, IL-6 and TNF-α, increased the expression of anti-inflammatory factor IL-10, and decreased the expressions of iNOS, CD80 and CD86, and increase the expressions of Arg1, CD206 and CD163. Further studies have revealed that SOCS1 activates autophagy by up-regulating the expression of TFEB, thereby inhibiting the polarization of M1 in macrophages. Furthermore, SOCS1 can promote the nuclear translocation of TFEB, while the phosphorylation of AMPK can up-regulate SOCS1 to promote the expression of TFEB. CONCLUSION: AMPK promotes nuclear transfer of TFEB by up-regulating SOCS1, thereby enhancing autophagy and inhibiting M1 polarization in macrophages, thus alleviating ALI.
GATA1 promotes TGF-β1-induced epithelial-mesenchymal transition by regulating GSDMB in human bronchial epithelial cells.
Li JJ, Chen JH, Yuan Y … +6 more , Li L, Zhou C, Chen H, Geng J, Cao Q, Jin R
Mol Immunol · 2025 Nov · PMID 41092691 · Publisher ↗
Asthma is a common inflammatory airway disorder characterized by recurrent cough, chest tightness, and dyspnea. The repeated inflammation of bronchial epithelial cells leading to epithelial-mesenchymal transition is beli...
Asthma is a common inflammatory airway disorder characterized by recurrent cough, chest tightness, and dyspnea. The repeated inflammation of bronchial epithelial cells leading to epithelial-mesenchymal transition is believed to play a pivotal role in airway remodeling associated with asthma. Gasdermin B (GSDMB), a member of the gasdermin family of structurally related proteins, has been identified as having a strong association with asthma. However, the precise role of GSDMB in asthma pathophysiology remains ambiguous. This study aimed to elucidate the biological function of GSDMB in asthma and its upstream regulatory mechanisms. Our findings demonstrated that GSDMB expression was also increased in human bronchial epithelial cells stimulated with transforming growth factor-β1 (TGF-β1). Overexpression of GSDMB resulted in an upregulation of intermediate mesenchymal markers following TGF-β1 treatment, thereby facilitating epithelial-mesenchymal transition (EMT) processes. Furthermore, GSDMB enhanced both proliferation and migration capacity in TGF-β1-treated Beas-2B cells. Notably, the transcription factor GATA1 was found to bind to the promoter region of GSDMB and facilitate its expression levels. These results indicate that the transcriptional axis involving GATA1/GSDMB exerts functions promoting EMT along with enhancing cellular proliferation and migration within TGF-β1-stimulated bronchial epithelial cells; suggesting that targeting GSDMB may represent a viable therapeutic strategy for managing asthma.
Role of efferocytosis in liver transplantation via hepatic macrophage.
Zhao M, Xu X, Peng H … +7 more , Tang C, Luo J, Liu J, Liu Z, Gong J, Gong J, Li J
Mol Immunol · 2025 Nov · PMID 41092690 · Publisher ↗
Liver transplantation has undergone progressive advancements since the 1960s, with optimized surgical techniques and improved outcomes resulting from standardized procedures and therapeutic regimens. However, postoperati...
Liver transplantation has undergone progressive advancements since the 1960s, with optimized surgical techniques and improved outcomes resulting from standardized procedures and therapeutic regimens. However, postoperative complications-such as ischemia-reperfusion injury, acute rejection, hepatocellular carcinoma recurrence, and biliary injury-continue to significantly affect both survival rates and quality of life in liver transplant recipients. Efferocytosis, the phagocytic clearance of apoptotic cells, plays a critical role in preventing necrosis-induced inflammation and promoting tissue resolution and repair. Accumulating evidence suggests that impaired efferocytosis is associated with several complications following liver transplantation. Although multiple hepatic cell types participate in efferocytosis, macrophages-notably Kupffer cells and monocyte-derived macrophages-are the primary mediators responsible for clearing apoptotic cells in the liver. Nevertheless, significant gaps remain in our understanding of how hepatic macrophages perform efferocytosis and whether defects in this process within donor-derived macrophages exacerbate post-transplant complications. This review provides a comprehensive discussion of efferocytosis, with a focus on its impact on liver transplantation-related complications. Furthermore, we explore the potential of targeting efferocytosis as a novel therapeutic strategy in liver transplantation.
Diosgenin ameliorates CLP-induced sepsis in mice via suppressing inflammatory responses and preserving intestinal mucosal barrier integrity.
Li Y, Zeng J, Zhong X … +7 more , Huang Q, Wang X, Sun S, Wang H, Huang X, Ling J, Lin R
Mol Immunol · 2025 Nov · PMID 41092689 · Publisher ↗
BACKGROUND: Diosgenin, a well-known steroid sapogenin, has demonstrated anti-inflammatory effects; however, its therapeutic potential for sepsis remains unclear. Intestinal barrier dysfunction is a critical contributor t...
BACKGROUND: Diosgenin, a well-known steroid sapogenin, has demonstrated anti-inflammatory effects; however, its therapeutic potential for sepsis remains unclear. Intestinal barrier dysfunction is a critical contributor to lethal sepsis, a systemic inflammatory response syndrome. This study investigated the protective effects of diosgenin on cecal ligation and puncture (CLP)-induced sepsis in mice, focusing on its impact on intestinal mucosal dysfunction and inflammation. Additionally, the effects of diosgenin on the expression of the endogenous antimicrobial peptide mCRAMP and the TLR4/MyD88 signaling pathway were investigated. METHODS: Sepsis was induced in male C57BL/6 mice via CLP. Survival rates were recorded, and serum and ileum tissue levels of TNF-α and IL-6 were quantified to assess the protective efficacy of diosgenin treatment. Intestinal barrier integrity was evaluated by hematoxylin and eosin (H&E) staining, while mucosal permeability was determined using serum D-lactic acid. Tight junction (TJ) proteins were detected via Western blotting. Immunohistochemistry was used to measure mCRAMP protein expression in the ileum, and quantitative real-time PCR (qRT-PCR) was employed to analyze the gene expression of mCRAMP, TLR4, and MyD88. Molecular docking was performed with Autodock4 software to predict the binding capacity between diosgenin and LL-37, TLR4 and MyD88. RESULTS: Diosgenin treatment significantly improve the survival of mice, decreased TNF-α and IL-6 production, and attenuated intestinal histopathological damage. Additionally, diosgenin decreased serum D-lactic acid levels, upregulated Claudin-1 and Occludin expression, and increased both mRNA and protein levels of mCRAMP while downregulating the gene expression of TLR4 and MyD88. Molecular docking analysis demonstrated favorable binding affinities of diosgenin to LL-37 (-6.3 kcal/mol), TLR4 (-8.3 kcal/mol), and MyD88 (-10.5 kcal/mol). All calculated binding energies were < -5.0 kcal/mol, suggesting potential effective binding of diosgenin to these targets. CONCLUSION: Diosgenin improved survival, suppressed inflammatory responses, and preserving intestinal mucosal barrier integrity in CLP-induced septic mice. These protective effects might involve alterations in mCRAMP expression and TLR4/MyD88 signaling.
The metabolic regulation of tumor-associated macrophage reprogramming.
Fan H, Lu D, Yin X … +9 more , Sun H, Wang Z, Sun H, Liu X, Li Y, Zhou Z, Chen L, Wang Y, Xin T
Mol Immunol · 2025 Nov · PMID 41092688 · Publisher ↗
Tumor-associated macrophages (TAMs) are an essential component of the immune cells that infiltrate the tumor microenvironment (TME) and exhibit immunosuppressive functions. These macrophages exhibit significant phenotypi...
Tumor-associated macrophages (TAMs) are an essential component of the immune cells that infiltrate the tumor microenvironment (TME) and exhibit immunosuppressive functions. These macrophages exhibit significant phenotypic plasticity and heterogeneity, highlighting their capacity to adapt to various environmental signals. This adaptability facilitates polarization shifts between pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes. As tumors proliferate and metastasize, the TME progressively transforms into an immunosuppressive environment. Consequently, TAMs undergo metabolic reprogramming in pathways such as glucose, lipid, and amino acid metabolism, among others, which ultimately drive the establishment of an immunosuppressive phenotype. While TAMs do not strictly conform to the M1 and M2 classifications, they often exhibit characteristics resembling M2 macrophages, thereby promoting tumor growth via immunosuppression. This review aims to elucidate the metabolic reprogramming of TAMs and investigate how they maintain their immunosuppressive phenotype, highlighting potential avenues for metabolic therapies.
Antibody preparation and immunological analysis of RBD from the SARS-CoV-2 Omicron BF.7 variant.
Wang Q, Wang C, Zhang Z … +10 more , Fan S, Lei P, Liu S, Li M, Wang K, Zhang Y, Kang L, Weng S, Kong L, Wang T
Mol Immunol · 2025 Nov · PMID 41061453 · Publisher ↗
The SARS-CoV-2 spike protein facilitates target recognition, cellular entry, and viral infection, leading to varying degrees of COVID-19 severity. Amino acid site mutations in the S protein RBD region can enhance the spr...
The SARS-CoV-2 spike protein facilitates target recognition, cellular entry, and viral infection, leading to varying degrees of COVID-19 severity. Amino acid site mutations in the S protein RBD region can enhance the spread and immune evasion of the SARS-CoV-2 Omicron variant. The study aimed to construct a prokaryotic expression vector for the S protein RBD of the SARS-CoV-2 Omicron BF.7 variant strain. Escherichia coli was used to express the RBD protein, and a polyclonal antibody was generated to investigate the immunological functions of the Omicron (BF.7) RBD. Optimization of expression conditions in Escherichia coli was conducted to achieve stable expression of pET-28a-BF.7-RBD, including induced temperature, induced time, and IPTG concentration. Serum antibody titers in RBD-immunized mice reached up to 1: 204800 as determined by indirect enzyme-linked immunosorbent assay. The polyclonal antibody could detect prokaryotic and eukaryotic RBD proteins, as well as commercial RBD proteins, and splenocytes were found to produce high levels of IFN-γ. This study successfully demonstrated the production of a large quantity of RBD protein with strong immunogenicity in E. coli, eliciting robust humoral and cellular immune responses in mice. The generation of high-potency polyclonal antibodies provides valuable insights for further research on the biological functions of the RBD protein, detection of Omicron variants, and vaccine development.
TNF-α and IFN-γ modulate the evasion of the immune response in primary mediastinal B-cell lymphoma.
Gršković P, Mihalić V, Krstulović A … +4 more , Möller P, Hančić S, Gašparov S, Korać P
Mol Immunol · 2025 Nov · PMID 41056747 · Publisher ↗
OBJECTIVES: Primary mediastinal B-cell lymphoma (PMBCL) is an aggressive type of non-Hodgkin lymphoma (NHL) that shares features with diffuse large B-cell lymphoma (DLBCL), but also with classical Hodgkin lymphoma (cHL)....
OBJECTIVES: Primary mediastinal B-cell lymphoma (PMBCL) is an aggressive type of non-Hodgkin lymphoma (NHL) that shares features with diffuse large B-cell lymphoma (DLBCL), but also with classical Hodgkin lymphoma (cHL). PMBCL often contains aberrations of genes involved in the immune response such as cREL and PD-L1, whose expression is also influenced by cytokines TNF-α and IFN-γ. METHODS: In this study, cell lines Farage, U2940, MedB-1 and Karpas1106p were used as PMBCL models and treated with different concentrations of TNF-α and IFN-γ over 24 and 48 h, followed by the quantification of cREL, CXCL10 and PD-L1 expression. Additionally, the expression of TNF-α, IFN-γ, cREL, CXCL10, CXCR3, PD-L1 and PD-1 genes was compared between PMBCL tissue samples and B-cell and T-cell rich zones of non-tumour tonsils. RESULTS: Prolonged exposure to TNF-α increased cREL expression, while IFN-γ strongly induced CXCL10 expression. The change in the expression of PD-L1 in response to the treatments differed across various cell lines. There was no statistically significant difference in the expression of the target genes between tumour and non-tumour patient tissue samples. CONCLUSIONS: the obtained results suggest that the immune checkpoints in PMBCL cells are affected by both their genetic profile and tumour microenvironment.
S1PR2-miR-212 feedback loop regulates allergic reactions.
Jeoung J, Jo H, Kim W … +1 more , Jeoung D
Mol Immunol · 2025 Nov · PMID 41056746 · Publisher ↗
We previously reported the anti-allergic effect of rocaglamide-A (roc-A). Molecular docking analysis showed the binding of roc-A to sphingosine-1-phospahe receptor 2 (S1PR2). This led us to hypothesize that S1PR2 might p...
We previously reported the anti-allergic effect of rocaglamide-A (roc-A). Molecular docking analysis showed the binding of roc-A to sphingosine-1-phospahe receptor 2 (S1PR2). This led us to hypothesize that S1PR2 might play a role in allergic reactions. Antigen stimulation increased the expression of S1PR2 in rat basophilic leukemia (RBL2H3 cells). Sphingosine-1-phosphate (S1P) increased the expression of S1PR2 in an antigen-independent manner. S1PR2 was necessary for both allergic reactions in vitro and anaphylaxis. Sphingosine prevented the antigen (DNP-HSA) from increasing the expression of S1PR2 and hallmarks of allergic reactions in RBL2H3 cells. Sphingosine also prevented antigen from increasing the level of reactive oxygen species (ROS). Animal model of passive systemic anaphylaxis (PSA) showed the increased expression of CXCL1. CXCL1 was shown to mediate allergic reactions in vitro. TargetScan predicted the binding of miR-212 to the 3 ´ UTR of S1PR2. The downregulation of S1PR2 prevented antigen from increasing the expression of CXCL1 at the transcriptional level. cmiR-212 was found to decrease the expression of S1PR2 in antigen stimulated RBL2H3 cells. miR-212 mimic decreased the luciferase activity associated with 3 ´ UTR of S1PR2. The miR-212 mimic exerted a negative effect on the passive cutaneous anaphylaxis (PCA). The downregulation of S1PR2 increased the expression of miR-212 in antigen stimulated RBL2H3 cells. This suggests that miR-212 and S1PR2 form negative feedback loops to regulate allergic reactions. Our results show that S1PR2-miR-212 negative feedback loop regulates allergic reactions in vitro and in vivo.
Protocatechuic aldehyde promotes diabetic wound healing by enhancing angiogenesis via H3K18 lactylation-mediated Acvr1c expression.
Fan W, You Y, Qu Y … +1 more , Liu G
Mol Immunol · 2025 Nov · PMID 41033083 · Publisher ↗
Delayed wound recovery is a major health issue affecting people with diabetes. Histone lactylation is involved in tissue repair. However, it is not clear whether protocatechuic aldehyde (PCA) promotes diabetic wound heal...
Delayed wound recovery is a major health issue affecting people with diabetes. Histone lactylation is involved in tissue repair. However, it is not clear whether protocatechuic aldehyde (PCA) promotes diabetic wound healing through histone lactylation. In this study, a diabetic wound mouse model was constructed to delve into the role of PCA in vivo. Chromatin immunoprecipitation sequencing (ChIP-seq) was used to determine genes affected by H3K18 lactylation (H3K18la) under PCA treatment. The effects and mechanisms of PCA on histone lactylation and angiogenesis were investigated through cellular experiments. We found that PCA accelerated wound healing and angiogenesis in diabetic mice, and significantly reduced the inflammatory response in wound tissues. Lactate and H3K18la levels were augmented in the model group in comparison with the control group, however, PCA treatment remarkably reversed their levels. ChIP-seq analysis revealed a significant enrichment of H3K18la at the Acvr1c locus, and this histone modification was downregulated by PCA treatment. PCA remarkably enhanced Acvr1c expression through H3K18la in HUVECs. Moreover, PCA treatment markedly elevated cell viability, migration and tube formation in comparison with the control group. However, this effect was counteracted by Acvr1c knockdown. In conclusion, PCA promoted HUVEC angiogenesis by increasing H3K18la-mediated Acvr1c expression, thereby promoting diabetic wound healing. This could offer a new treatment approach to enhance the effectiveness of healing diabetic wounds.
The mechanism of SMAD4/ERK pathway in regulating Th17/Treg cell differentiation leading to olfactory dysfunction in chronic rhinosinusitis.
Cao S, Niu Y, Ning J … +3 more , Wen N, Chen R, Wu H
Mol Immunol · 2025 Nov · PMID 41004934 · Publisher ↗
BACKGROUND: Chronic rhinosinusitis (CRS) is characterized by a high recurrence rate within five years post-surgery, posing a persistent challenge for otolaryngologists globally. Recent research has underscored the pivota...
BACKGROUND: Chronic rhinosinusitis (CRS) is characterized by a high recurrence rate within five years post-surgery, posing a persistent challenge for otolaryngologists globally. Recent research has underscored the pivotal role of the Th17/Treg cell balance in the pathogenesis of CRS. This study aims to investigate the alterations in the Th17/Treg cell balance in CRS and elucidate the underlying molecular mechanisms. METHODS: CRS model was established to assess the levels of inflammatory cytokines, olfactory marker protein expression, SMAD4 expression, and ERK1/2 phosphorylation. We then overexpressed SMAD4 or treated CRS mice with ERK1/2 inhibitors, measuring the impact on Th17/Treg marker expression. Moreover, the influence of the SMAD4/ERK signaling axis on the Th17/Treg balance within the CD4 + T cell population was investigated. RESULTS: CRS mice exhibited significantly reduced olfactory marker protein and SMAD4 expression, alongside increased ERK1/2 phosphorylation. Histological analysis revealed an increased infiltration of eosinophils. Of particular note, the expression of Treg markers was markedly decreased, while Th17 marker expression exhibited a corresponding increase, suggesting a potential shift in the Th17/Treg balance. Interventions involving SMAD4 overexpression or ERK1/2 inhibition led to a reduction in eosinophil infiltration and successfully reversed the aberrant expression patterns of the aforementioned markers. Furthermore, SMAD4 knockdown resulted in a decreased proportion of Treg cells and an increased proportion of Th17 cells. This alteration in the Th17/Treg balance was effectively counteracted by ERK inhibitor. CONCLUSIONS: The deletion of SMAD4 regulates the differentiation of Th17/Treg cells via ERK1/2 phosphorylation, thereby exacerbating the olfactory dysfunction of CRS.
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