Ask about this productRelated genes to: TNFRSF4 Blocking Peptide
- Gene:
- TNFRSF4 NIH gene
- Name:
- TNF receptor superfamily member 4
- Previous symbol:
- TXGP1L
- Synonyms:
- ACT35, OX40, CD134
- Chromosome:
- 1p36.33
- Locus Type:
- gene with protein product
- Date approved:
- 1994-12-15
- Date modifiied:
- 2019-04-23
Related products to: TNFRSF4 Blocking Peptide
Related articles to: TNFRSF4 Blocking Peptide
- Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation and destruction. Identifying novel therapeutic targets is crucial for improving RA treatment. This study aimed to identify immune-related biomarkers in RA and investigate the potential of CD27 as a therapeutic target. We employed bioinformatics analysis of gene expression data from RA patients and healthy controls (GSE55457), followed by machine learning approaches (LASSO regression and Boruta algorithm) to identify potential biomarkers. Findings were validated in an independent dataset (GSE55235). The therapeutic potential of CD27 neutralization was evaluated in a collagen-induced arthritis (CIA) mouse model. Mechanisms were explored through quantitative real-time PCR, Western blot analysis, ELISA, and flow cytometry to assess T cell subsets, cytokine profiles, and signaling pathways. Bioinformatics analysis identified 714 differentially expressed genes, and machine learning analyses identified CD27, CD24, TNFRSF4, and PDCD1LG2 as potential RA biomarkers, all demonstrating strong diagnostic performance. CD27 showed significant positive correlations with T lymphocyte infiltration. In the CIA model, CD27 neutralization significantly reduced arthritis severity scores. This therapeutic effect was associated with suppression of Th1 responses, evidenced by significantly decreased serum levels of Th1 cytokines (IFN-γ, IL-2, TNF-α) and reduced CD4 + IFN-γ + cell populations, while Th2-related cytokines (IL-4, IL-5) remained largely unaffected. Mechanistically, CD27 neutralization attenuated phosphorylation of AKT and NF-κB p65 in vivo, while p38 MAPK remained unchanged. In vitro, recombinant CD27 protein stimulation of naive CD4 + T cells promoted Th1-biased differentiation, increasing CD4 + IFN-γ + cells and enhancing the phosphorylation of NF-κB p65 and AKT. Our study identifies CD27 as a potential therapeutic target in RA. CD27 neutralization attenuates arthritis severity by suppressing Th1 responses, possibly through modulation of AKT and NF-κB signaling pathways. These findings provide new insights into RA pathogenesis and suggest CD27 as a promising target for RA treatment. - Source: PubMed
Publication date: 2026/04/25
Lu AnghanPu LuqiaoTian YadanSong JiaxinLuo DingxiaWu Jingjin - Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutant lung adenocarcinoma (LUAD) typically demonstrates limited response to neoadjuvant immunotherapy (NIT). Elucidating the immune determinants that differentiate responders from non-responders was critical for optimizing immunotherapy strategies. This study aimed to characterize the tumour microenvironment features of KRAS-mutant LUAD following neoadjuvant programmed death protein 1 (PD-1) inhibitor therapy by integrating clinical outcomes with single-cell RNA sequencing (scRNA-seq). - Source: PubMed
Wu SikaiNiu JihengChen XiaoweiLi JinfeiTang QuanyingYang ZhenlinGao Shugeng - Prior studies in ichthyosis have demonstrated cutaneous and/or systemic immune abnormalities with barrier defects; however, the transcriptomes of the major orphan forms of ichthyosis have yet to be characterized through tape-stripping, a minimally invasive sampling method validated in other inflammatory skin diseases. Skin tape strips from 27 patients with ichthyosis (9 Netherton syndrome/NS, 6 congenital ichthyosiform erythroderma/CIE, 7 lamellar ichthyosis/LI, 5 epidermolytic ichthyosis/EI) and 18 demographically matched healthy controls were analyzed with RNA-seq. Differential expression was defined as fold change>2 and false-discovery rate<0.05. All subtypes shared significant Th17/Th22 upregulation (e.g. S100A7/8/9, PI3, CCL20), and Th2 products (e.g. TNFRSF4, IL13, CCR4) were particularly increased in NS. Tape strips additionally captured common increases in Th1 (IL1B, OASL), and IL4R upregulation in NS, LI, and EI. While modulation of lipid markers was variable across subtypes, several epidermal differentiation complex/cornified envelope (EDC-CE) genes were increased in all or most subtypes. Disease-severity metrics were moderately correlated with increases in ceramide synthase CERS3 and Th17/Th22 and late cornified envelope markers. Changes in immune and EDC-CE tape-strip markers correlated significantly and positively with those measured in biopsies. Our findings highlight tape-stripping as a minimally invasive approach to profile ichthyosis, which could provide future pathogenic and therapeutic insights. - Source: PubMed
Publication date: 2026/04/09
Kim MadelineManson MeredithLiu YingRangel StephanieKaplan NihalRabbaa LydiaChoate KeithBose SwaroopMetukuru RagasrutiLin XinyiLargen JosephShah ManaliEstrada Yeriel DPaller Amy SGuttman-Yassky Emma - Allergic conjunctivitis (AC) is an inflammatory ocular condition triggered by allergens like pollen. Although general allergic mechanisms are well characterized, the immune specificity of the ocular mucosa remains unclear. This study investigates immune-related mRNAs and circRNAs to uncover novel molecular pathways in AC pathogenesis. Using a ragweed pollen-induced murine AC model, conjunctival tissues were subjected to RNA sequencing. DESeq2-based differential expression analysis revealed dysregulated mRNAs and circRNAs, with significant enrichment in the IL-17 signaling pathway. Key IL-17-associated genes (, , ) and co-expressed circRNAs (Circ9626, Circ2598, etc.) were markedly upregulated. Immune infiltration analysis confirmed a mixed Th2/Th17 response with notable neutrophil involvement. These findings highlight the potential involvement of the Th17/IL-17 axis beyond classical Th2 immunity and construct a putative circRNA-IL-17 co-expression network, providing a comprehensive transcriptomic landscape and identifying potential candidates for future therapeutic exploration in AC. - Source: PubMed
Publication date: 2026/03/06
Zhang HongyuQi YanLeng QingQin YaningZhang HongWu Bing - OX40 (CD134), a key member of the tumor necrosis factor receptor superfamily, provides an indispensable co-stimulatory signal for T cell activation. This review systematically elucidates the molecular biology of the OX40/OX40L significant synergistic efficacy signaling axis and its multifaceted roles and significant potential in cancer immunotherapy. This pathway, through the activation of NF-κB, PI3K/Akt, and other signaling cascades, promotes the proliferation, survival, and function of effector T cells while effectively inhibiting regulatory T cell (Treg) function and remodeling the immunosuppressive tumor microenvironment (TME), thereby exerting potent anti-tumor effects. However, the prognostic value of OX40 expression is tumor-type specific, and although monotherapy clinical trials have confirmed its favorable safety profile, the objective response rates remain limited. Importantly, the interpretation of OX40 expression must consider its cellular compartment-whether it is expressed on effector T cells or Tregs-as these subsets exert opposing immune functions. Furthermore, whether OX40 is a causal driver of anti-tumor immunity or merely a surrogate marker of an inflamed TME remains an open question that impacts its therapeutic targeting. This has driven a comprehensive shift in research focus towards combination therapies. Currently, various combination strategies (e.g., with immune checkpoint inhibitors, radiotherapy, cell therapies, and metabolic modulators) and the development of next-generation agonists (such as hexavalent antibodies and bispecific molecules) are demonstrating significant synergistic efficacy in preclinical studies and early-phase trials. Despite challenges including the lack of precise biomarkers and the difficulty in reversing the immunosuppressive TME, optimized combination regimens, innovative drug design, and the utilization of the neoadjuvant treatment window hold promise for breakthroughs in precision immunotherapy targeting OX40 within the future landscape of comprehensive cancer treatment. - Source: PubMed
Publication date: 2026/03/06
Wei YingYingLu LeZhao RouBie QingliHe BaoyuZhang Bin