Cellular & Molecular Immunology[JOURNAL]
Sun
200 papers
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.
Inhibition of RNase L enhances the expression efficiency of mRNA-LNPs.
Nguyen HM, Cassaidy B, Collinge M … +5 more , Hickey JC, Li J, Arellano-Saab A, Kumpf SW, Thorn M
Mol Immunol · 2026 Feb · PMID 41564652 · Publisher ↗
mRNA-LNPs offer a promising platform for therapeutic protein expression, however, achieving efficient and sustained translation remains a significant challenge. One of the major barriers to mRNA-LNP efficacy is the activ...
mRNA-LNPs offer a promising platform for therapeutic protein expression, however, achieving efficient and sustained translation remains a significant challenge. One of the major barriers to mRNA-LNP efficacy is the activation of innate immune responses that recognize foreign RNA and suppress subsequent protein synthesis. Among these, the OAS-RNase L pathway, involved in degradation of cytoplasmic mRNA, plays a key role. This study examined the impact of RNase L and RNase L blockade on mRNA-LNP expression efficiency. In THP-1 cells, which express high endogenous levels of RNase L, both genetic ablation and pharmacological inhibition of RNase L led to a marked increase in protein expression. In contrast, HeLa cells, which exhibit low RNase L expression, showed minimal response to RNase L inhibition. In human peripheral blood mononuclear cells (PBMCs), RNase L inhibition also enhanced mRNA expression, while blocking other RNA sensors such as TLR7/8, RIG-I, TLR3, or MAVS, did not. Activation of the OAS-RNase L pathway may be driven by double-stranded secondary structure formed by therapeutic mRNA, resulting in mRNA recognition and degradation. RNase L acts as a key post-transcriptional regulator of mRNA stability and translation. Targeting this pathway offers a strategy to improve the performance of mRNA-based therapeutics.
Liquiritigenin regulates JAK/STAT3 and NF-κB signaling pathways to reduce colonic damage and barrier dysfunction caused by a high-salt diet.
Yan W, Wang L, Zhu W … +7 more , Liu X, Xu Z, Liu J, Ding J, Zhu M, Ma F, Dong Z
Mol Immunol · 2026 Feb · PMID 41558083 · Publisher ↗
It has been shown that a high-salt diet (HSD) significantly damages the colonic epithelial barrier, resulting in increased intestinal permeability, upset gut microbial balance, and generalized inflammation. Despite this,...
It has been shown that a high-salt diet (HSD) significantly damages the colonic epithelial barrier, resulting in increased intestinal permeability, upset gut microbial balance, and generalized inflammation. Despite this, effective therapeutic strategies to prevent HSD-induced intestinal damage remain limited. This study aims to explore the preventive properties and basic mechanisms of liquiritigenin (LG)，a natural flavonoid, against chronic colonic injury induced by prolonged HSD exposure. A murine model of chronic colitis was established by administering an 8 % NaCl diet, and LG therapy was used to evaluate how it affected the function of the intestinal barrier and allergic reactions. The development of pro- and anti-inflammatory cytokines (il-β, il-6, tnf-α, il-10, and inos) as well as important tight junction proteins (ZO-1, Claudin-3, and Occludin) was assessed. Furthermore, we investigated the molecular processes in vitro using normal colonic epithelial cell line NCM-460, with particular focus on the NF-κB and JAK/STAT3 signaling pathways. LG increased the expression of junction-binding proteins, greatly enhanced the intestinal wall integrity, and mitigated histopathological damage. Furthermore, it markedly attenuated excessive inflammatory responses both in vivo and in vitro. Mechanistically, LG suppressed the phosphorylation of key components within the pathways of JAK/STAT3 and NF-κB, thereby inhibiting downstream inflammatory signaling and epithelial cell injury. Collectively, these results demonstrate that liquiritigenin exerts protective effects against HSD-induced colonic damage by concurrently modulating the NF-κB and JAK/STAT3 pathways, highlighting its therapeutic potential for high salt-related intestinal disorders.
Liposome-mediated simvastatin in vaccine adjuvants: Its application and mechanism.
Chen Z, Xia Z, Chen L … +15 more , Nie Q, Gong W, Cao W, Wang X, Zou Y, Zhang S, Yang Y, Yang M, Yang J, Liu Y, Zhang L, Fang W, Chen Y, Zhao J, Meng Z
Mol Immunol · 2026 Feb · PMID 41539277 · Publisher ↗
To mitigate the APC cytotoxicity associated with simvastatin (a promising adjuvant candidate), we encapsulated this drug in liposomes to generate LIPO-SIM, and explored the potential and mechanism. Formulated via ethanol...
To mitigate the APC cytotoxicity associated with simvastatin (a promising adjuvant candidate), we encapsulated this drug in liposomes to generate LIPO-SIM, and explored the potential and mechanism. Formulated via ethanol injection and rotary evaporation, liposome-SIM was characterized for appearance, ζ-average, PDI, zeta potential, and encapsulation efficiency. C57BL/6 J mice were immunized with LIPO-SIM + OVA (0/21-day schedule), euthanized on day 28 to evaluate immunogenicity, safety, and antigen presentation mechanisms. In vitro, DC2.4 cells stimulated with liposome-SIM underwent RNA-Seq, metabolomics, and western blotting to clarify adjuvant mechanisms. Results showed liposome-SIM significantly increased anti-OVA IgG titers and cellular immunity, activated local lymph node macrophages/dendritic cells, and enhanced MHC-I presentation. In vitro, AMPK inhibition and NF-κB activation were observed. No organ toxicity or inflammatory storms were detected. Liposome-SIM enhances cellular immunity via the MHC-I pathway, with AMPK/NF-κB signaling as a potential key mechanism.
HSPH1 and DNAJB1 as potential key regulators in hepatic ischemia-reperfusion injury.
Wu S, Zhou W, Duo H … +7 more , You J, Chen Y, Du S, Ku N, Luo J, Liu Z, Ye Q
Mol Immunol · 2026 Feb · PMID 41534252 · Publisher ↗
Hepatic ischemia-reperfusion injury (HIRI) is a common and inevitable pathological event during liver transplantation and hepatectomy, which significantly impairs postoperative liver function recovery and patient prognos...
Hepatic ischemia-reperfusion injury (HIRI) is a common and inevitable pathological event during liver transplantation and hepatectomy, which significantly impairs postoperative liver function recovery and patient prognosis. However, the molecular and cellular mechanisms of HIRI have not been fully elucidated and further research is urgently needed. In recent years, the rapid development of bioinformatics analysis technology and the research method combining multi-dimensional data mining with experimental verification have become important strategies for exploring the mechanisms of complex diseases. Building on this, this study aims to screen and analyze the potential roles and mechanisms of key regulatory factors in the process of HIRI through systematic bioinformatics analysis and experimental verification, providing a basis for clarifying its pathogenesis and finding potential therapeutic targets. In this study, two transcriptome microarray datasets (GSE14951 and GSE7706) of human liver tissue were systematically analyzed, and candidate genes related to IRI were initially screened through differential expression analysis. Combined with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, protein-protein interaction (PPI) network construction and modular analysis were performed to identify potential key regulatory factors, ultimately highlighting HSPH1 and DNAJB1. Subsequently, based on a mouse liver IRI model, paired reperfusion tissue samples from clinical liver transplant patients, and an AML12 cell hypoxia/reoxygenation (H/R) model, the two genes were experimentally validated from multiple perspectives, including transcriptional expression, protein levels, and subcellular localization. A combination of quantitative PCR (qPCR), Western blotting, immunohistochemistry (IHC), immunofluorescence (IF), and co-immunoprecipitation (Co-IP) was employed to comprehensively evaluate their expression dynamics, subcellular distribution, and protein-protein interaction characteristics. Differential expression analysis identified 154 genes with consistent expression trends across the two datasets, which were significantly enriched in metabolic, stress response, inflammatory, and protein folding pathways. PPI network construction and module analysis further identified HSPH1 and DNAJB1 as core components of a heat shock protein interaction cluster. Validation using a mouse IRI model, paired reperfusion tissue samples from clinical liver transplant patients, and an AML12 cell hypoxia/reoxygenation (H/R) model demonstrated that both genes were significantly upregulated under IRI conditions, localized in the cytosol, and exhibited co-localization and physical interaction. Transcription factor prediction analysis suggested that STAT3 and NR1I2 might be involved in their transcriptional regulation. In conclusion, HSPH1 and DNAJB1 are co-expressed and physically interact in hepatic IRI, suggesting that they may be involved in the regulation of protein homeostasis and cellular stress responses related to liver IRI, providing important experimental evidence for a deeper understanding of the molecular characteristics of liver IRI.
NSUN2 aggravates M1 macrophage polarization in arthritis progression through m5C modification of CCL2.
He C, Zhang J, Deli G … +5 more , Zhao K, Liu L, Lai B, Hu M, He H
Mol Immunol · 2026 Feb · PMID 41506006 · Publisher ↗
BACKGROUND: Arthritis is an inflammatory disease characterized by multifactorial pathogenesis in joints or surrounding tissues. M1 macrophage polarization is a key pathological feature of arthritis, and m⁵C RNA modificat...
BACKGROUND: Arthritis is an inflammatory disease characterized by multifactorial pathogenesis in joints or surrounding tissues. M1 macrophage polarization is a key pathological feature of arthritis, and m⁵C RNA modification has been implicated in disease progression. This study aimed to elucidate the role of NSUN2, a writer of m⁵C modification, in modulating arthritis development. METHODS: LPS-stimulated RAW264.7 cell models and collagen-induced arthritis (CIA) rat models were established. M1 and M2 macrophage polarization was assessed by detecting cell surface markers and pro-inflammatory cytokines using immunofluorescence, enzyme-linked immunosorbent assay (ELISA), Western blot, and quantitative real-time PCR. Underlying mechanisms were investigated via methylated RNA immunoprecipitation (MeRIP), Co-immunoprecipitation (Co-IP), and Dual-Luciferase reporter assays. RESULTS: Downregulation of NSUN2 significantly inhibited M1 polarization and promoted M2 activation both in vitro and in vivo. NSUN2 enhanced m5C modification of CCL2, stabilized its mRNA expression, and facilitated its interaction with CCR2. Furthermore, NSUN2 activated the NF-κB signaling pathway in macrophages. Notably, inhibition of CCL2 activity abrogated the effects of NSUN2 on macrophage polarization. CONCLUSION: NSUN2 drives M1 macrophage polarization through m5C modification of CCL2, thereby exacerbating arthritis progression. Targeting NSUN2 may alleviate inflammatory responses, offering a novel therapeutic strategy for arthritis treatment.
Acupuncture alleviates premature ovarian insufficiency via Rictor/mTOR pathway in mice by stimulating the Guanyuan acupoint.
Luo Y, Chen Y, Huang S … +6 more , Zhu H, Zhao T, Feng S, Ma F, Ning Y, Wu J
Mol Immunol · 2026 Feb · PMID 41506005 · Publisher ↗
Acupuncture is a popular therapeutic therapy for premature ovarian insufficiency (POI). The specific effect and the underlying mechanism of Guanyuan acupoint on the ovarian function of POI model mice remain unclear. The...
Acupuncture is a popular therapeutic therapy for premature ovarian insufficiency (POI). The specific effect and the underlying mechanism of Guanyuan acupoint on the ovarian function of POI model mice remain unclear. The female C57BL6 mice were injected peritoneally with 12 mg/kg busulfan and 120 mg/kg cyclophosphamide to induce POI. The acupuncture intervention at Guanyuan acupoint was performed on the second day after the modeling. Vaginal smears were used to monitor the estrous cycle. The hematoxylin and eosin (H&E) staining was used to observe the morphological changes of ovarian tissue, and the TUNEL fluorescence staining assay was carried out to detect the apoptotic level of granulosa cells. The sex hormone levels were monitored as well. RNA sequencing was performed to select candidate gene which was regulated by acupuncture. Finally, the upstream lactating modification mechanism of Rictor was further investigated. The results showed that acupuncture at Guanyuan acupoint increased the number of vaginal exfoliated cells and inhibited the apoptosis of granulosa cell in POI model mice. Sex hormone levels indicated a marked decrease in AMH and E in POI group, with a concurrent significant rise in FSH levels. Furthermore, the Rictor/mTOR pathway was inactivated in POI model group, while was prominently activated by acupuncture at Guanyuan acupoint. Acupuncture intervened H3K18la to increase Rictor promoter activity in POI. In conclusion, acupuncture at Guanyuan acupoint increased body and ovarian weight, improved ovarian tissue morphology and structure, improved follicle development, and regulated ovarian function in POI model mice. This might be related to the activation of the Rictor/mTOR pathway.
Investigating the role of SMOX in rheumatoid arthritis.
Jiang Z, Zhang R, Han Y … +7 more , Sun R, Kong M, Zhang Y, Li J, Song G, Qiao L, Wang L
Mol Immunol · 2026 Jan · PMID 41485416 · Publisher ↗
Rheumatoid arthritis (RA) is pathologically marked by joint inflammation and damage. Although the association between spermidine and RA has been recognized, the precise contribution of spermine oxidase (SMOX)-the enzyme...
Rheumatoid arthritis (RA) is pathologically marked by joint inflammation and damage. Although the association between spermidine and RA has been recognized, the precise contribution of spermine oxidase (SMOX)-the enzyme catalyzing spermidine synthesis-to RA pathogenesis remains undefined. It's observed in this study that SMOX was responsible for inflammatory stimuli that its expression increased obviously when RA-associated fibroblast-like synoviocytes (FLSs) were challenged by inflammatory factors. Functionally, silencing SMOX could inhibit migration, invasion, and cytokine production, but induced apoptosis of RA-FLS. Moreover, inhibition of SMOX using JNJ-9350 yielded anti-inflammatory effects comparable to those achieved by gene silencing in RA-FLS. In vivo experiments demonstrated that JNJ-9350 could effectively reduce the severity of arthritis, minimize histopathological damage, and prevent bone erosion in collagen antibody-induced arthritis (CAIA) mice. The present results indicate that SMOX is implicated in the development of RA and suggest that targeting SMOX could be a novel treatment strategy.
An H₂S-releasing oridonin derivative protects HaCaT cells against metabolic stress via PI3K/AKT/Nrf2 signaling.
Lin L, Jia Y, Xue R … +4 more , Shi Y, Li D, Xu F, Chu C
Mol Immunol · 2026 Feb · PMID 41483658 · Publisher ↗
The chronic hyperglycemia and its-associated metabolic changes often lead to impaired wound healing, which seriously affects the quality of life of diabetic patients. Oxidative stress and apoptosis are key factors that i...
The chronic hyperglycemia and its-associated metabolic changes often lead to impaired wound healing, which seriously affects the quality of life of diabetic patients. Oxidative stress and apoptosis are key factors that impede epidermal cell proliferation and migration and delay wound healing. The aim of this study was to investigate the protective effect of a novel hydrogen sulfide (HS)-releasing oridonin derivative (OAc-Ph-ADT) on epidermal HaCaT cells against a high-glucose and high-fat environment in vitro. Mechanistic studies showed that OAc-Ph-ADT exerted its antioxidant effects by activating the PI3K/AKT/Nrf2 signaling pathway. Specifically, it increased PI3K and phosphorylated-AKT expression, and promotes Nrf2 nuclear translocation, which in turn enhances the mRNA and protein expression of downstream antioxidant factors (HO-1, SOD2 and NQO1). In addition, OAc-Ph-ADT significantly reduced apoptosis by inhibiting the decrease in mitochondrial membrane potential and decreasing the expression of apoptosis-related proteins (Bax, Cleaved-Caspase 3/9). It was also observed that OAc-Ph-ADT up-regulated the expression of cystathionine β-synthase (CBS) via Nrf2, which further promoted the synthesis of endogenous HS, resulting in positive feedback regulation. In summary, this paper elucidated through systematic in vitro experiments that OAc-Ph-ADT has a protective effect against epidermal cell damage in a high-glucose and high-fat environment, revealing its potential as a candidate molecule for diabetic wound treatment, and this novel HS-releasing oridonin derivative has a potential application as a diabetic wound healing promoter.
Hippo signaling as a therapeutic switch for T cell functions and tumor immunity.
Fan J, Riaz F, Pan F
Mol Immunol · 2026 Feb · PMID 41483657 · Publisher ↗
The Hippo signaling pathway is a fundamental regulator of organ growth, tissue regeneration, and cellular homeostasis, with far-reaching implications in cancer biology and immunology. Dysregulation of this pathway, parti...
The Hippo signaling pathway is a fundamental regulator of organ growth, tissue regeneration, and cellular homeostasis, with far-reaching implications in cancer biology and immunology. Dysregulation of this pathway, particularly through its downstream effectors YAP (Yes-associated protein) and TAZ (transcriptional co-activator with PDZ-binding motif), is closely associated with oncogenic transformation and the establishment of an immunosuppressive tumor microenvironment (TME). This review discusses current knowledge on the multifaceted roles of Hippo signaling in cancer, focusing on its interactions with T cell-mediated immunity and mechanisms of tumor immune regulation. Aberrant YAP/TAZ activation enhances cancer cell proliferation, remodels the TME, and reprograms immune responses to favor tumor growth and immune evasion. The review explores how modulation of Hippo pathway components influences both tumor progression and immune cell function, highlighting its central role in shaping anti-tumor immunity. Furthermore, the therapeutic potential of targeting YAP/TAZ signaling is discussed in the context of advancing precision medicine and improving immunotherapeutic outcomes. Collectively, this work highlights the Hippo signaling cascade as both a key driver of tumorigenesis and a crucial regulator of immune modulation. A comprehensive understanding of its molecular interactions with T cells and the TME will support the development of innovative YAP/TAZ-targeted strategies that integrate molecular signaling and immune modulation, offering new directions for effective cancer therapy.
Formononetin in Jiawei Qihuangyin inhibits podocyte epithelial-mesenchymal transition and ameliorates diabetic nephropathy via SIRT1/NF-κB axis.
Li H, Ke J, Zhou Y … +4 more , Chen H, Wu X, Liu H, Li J
Mol Immunol · 2026 Feb · PMID 41483656 · Publisher ↗
BACKGROUND: Traditional Chinese medicine (TCM) has shown great promise in treating diabetic nephropathy (DN). However, the key targets and mechanisms underlying the therapeutic effects of the active ingredients of modifi...
BACKGROUND: Traditional Chinese medicine (TCM) has shown great promise in treating diabetic nephropathy (DN). However, the key targets and mechanisms underlying the therapeutic effects of the active ingredients of modified prescription Jiawei Qihuangyin (JWQHY) remain unclear. METHODS: Network pharmacology analysis was employed to identify potential targets of JWQHY in DN. Protein-protein interaction (PPI) and TCM component-target networks were constructed, and KEGG pathway enrichment analysis was performed to determine key therapeutic targets and signaling pathways. Molecular docking suggested an interaction between the major active compound formononetin (FMN) and the central target silent information regulator 1 (SIRT1), which was experimentally validated using cellular thermal shift assay. SIRT1 expression in podocytes was assessed by qRT-PCR and western blotting (WB). Cell viability (CCK-8), apoptosis (flow cytometry), and proinflammatory cytokine secretion (ELISA) were measured to evaluate podocyte injury. The acetylation level of NF-κB p65 and epithelial-mesenchymal transition (EMT)-related proteins were analyzed by WB. In vivo, a DN rat model was established to assess the therapeutic efficacy of JWQHY through biochemical urine analysis, histopathological examination (HE staining), and WB detection of SIRT1, acetylated NF-κB p65, and EMT markers. RESULTS: Network pharmacology identified 52 potential overlapping targets of JWQHY in DN, primarily associated with the NF-κB pathway. Among these, SIRT1 was predicted and experimentally confirmed as the main target of FMN. In a high-glucose-induced podocyte injury model, FMN upregulated SIRT1 expression, promoted NF-κB p65 deacetylation, and inhibited podocyte EMT. Consistently, FMN treatment improved renal function, reduced podocyte injury, and modulated SIRT1/NF-κB signaling in DN rats. CONCLUSION: JWQHY exerts therapeutic effects in diabetic nephropathy by modulating the SIRT1/NF-κB signaling axis through its active compound formononetin, thereby inhibiting podocyte EMT. These findings provide mechanistic insight into the pharmacological basis of FMN and support its clinical potential in DN treatment.
CXCL2-TLR4 axis activates NETs by accelerating autophagy through ATG7 to promote the progression of idiopathic interstitial pneumonia.
He J, Li J, Bai M … +1 more , Yang J
Mol Immunol · 2026 Jan · PMID 41443150 · Publisher ↗
OBJECTIVE: This study aimed to elucidate the molecular mechanisms through which CXCL2 contributes to the pathogenesis of idiopathic interstitial pneumonia (IIP). METHODS: Neutrophils were isolated, and the formation of n...
OBJECTIVE: This study aimed to elucidate the molecular mechanisms through which CXCL2 contributes to the pathogenesis of idiopathic interstitial pneumonia (IIP). METHODS: Neutrophils were isolated, and the formation of neutrophil extracellular traps (NETs) was assessed after CXCL2 treatment. Cellular concentrations of cell-free DNA (cf-DNA) were quantified via a cf-DNA/NET kit. Additionally, an enzyme-linked immunosorbent assay (ELISA) was used to measure the expression levels of IL-6, TNF-α, and LL-37. Western blot analysis was used to measure the levels of LC3-II, LC3-I, citrullinated histone H3 (citH3), myeloperoxidase (MPO), and elastase. Immunohistochemistry was conducted to measure cit H3 levels. Pathological alterations in the lung tissue were examined via microscopic hemosiderin and eosin staining. RESULTS: CXCL2 treatment significantly increased the cellular expression levels of cf-DNA, IL-6, TNF-α, and LL-37, as well as cit H3 and MPO, which are markers of NETs. Furthermore, CXCL2 treatment induced a substantial increase in cellular autophagy. Additionally, CXCL2 treatment led to marked upregulation of TLR4 expression and further elevation of autophagy levels, accompanied by increases in cf-DNA, IL-6, TNF-α, and LL-37 expression. Inhibition of TLR4 expression significantly reduced the levels of these factors. Moreover, the CXCL2-induced upregulation of cf-DNA, IL-6, TNF-α, LL-37, cit H3, and MPO was notably suppressed following the knockdown of ATG7. In IIP murine models, there was a significant upregulation of cf-DNA, IL-6, TNF-α, and LL-37, as well as an increase in cit H3 and MPO expression. Lung tissue analysis revealed inflammatory cell infiltration, alveolar wall thickening, tissue congestion, and edema. Inhibition of CXCL2 and TLR4 expression significantly ameliorated these pathological changes. CONCLUSIONS: The CXCL2TLR4 axis may facilitate NET activation by promoting autophagy via ATG7, thereby contributing to IIP progression.
Silence of circPLK1 inhibits NSCLC progression by regulating the miR-1294/SLC16A9 axis.
Li C, Yang Y, Li Q … +4 more , Wang G, Tao T, Li L, Sang H
Mol Immunol · 2026 Jan · PMID 41443149 · Publisher ↗
BACKGROUND: Non-small cell lung cancer (NSCLC) is the malignancy with the highest mortality worldwide. Circular RNA polo-like kinase 1 (circPLK1) is a circular RNA that involved in cancer progression. However, the role o...
BACKGROUND: Non-small cell lung cancer (NSCLC) is the malignancy with the highest mortality worldwide. Circular RNA polo-like kinase 1 (circPLK1) is a circular RNA that involved in cancer progression. However, the role of circPLK1 in NSCLC requires further investigation. METHODS: The expression of circPLK1 in NSCLC cells was measured by using qRT-PCR. Bioinformatics analysis was performed to identify miRNAs that bind to circPLK1 and the target mRNAs of these miRNAs. Cell viability, proliferation, apoptosis, migration, and invasion were assessed using CCK-8, colony formation, flow cytometry, and Transwell assays, respectively. Protein expression was evaluated by western blotting. Xenograft models were established to verify the regulatory role of circPLK1 in the miR-1294/SLC16A9 axis. RESULTS: circPLK1 was upregulaterd in NSCLC cells. Silencing circPLK1 markedly inhibited cell viability, proliferation, migration, and invasion, while accelerating apoptosis in NSCLC cells. circPLK1 acted as a sponge for miR-1294 and promoted SLC16A9 expression in NSCLC cells. Knockdown of circPLK1 suppressed tumor growth in NSCLC by regulating the miR-1294/SLC16A9 axis. CONCLUSION: circPLK1 silence inhibited the proliferation, migration, and invasion of NSCLC cells by regulating the miR-1294/SLC16A9 axis.
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