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Assessing the causality of interferon-γ and its receptor 1/2 with systemic lupus erythematosus risk using genetic data

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Rheumatology & Autoimmunity 2024年第2期4卷 109-118页

作者： Minjing Chang Kaixin Yao Jiawei Hao Yinqi Long Lulin Qiao Yaru Zhang Kexin Ma Peifeng He Shanxi Key Laboratory of Big Data for Clinical Decision Shanxi Medical UniversityTaiyuanShanxiChina Ministry of Education Key Laboratory of Cellular Physiology at Shanxi Medical UniversityTaiyuanShanxiChina Institute of Medical Data Sciences Shanxi Medical UniversityTaiyuanShanxiChina

Background::The interferon-γ (IFN-γ) signaling pathway is activated in systemic lupus erythematosus (SLE). This study aimed to assess the causal association between IFN-γ, IFN-γ receptor 1 (IFN-γR1), and IFN-γR2 and SLE using a bidirectional Mendelian randomization (MR) ***::Genetic instruments for exposure to IFN-γ, IFN-γR1, and IFN-γR2 were derived from a large genome-wide association study (GWAS) that included a sample size of 3301 participants. Instrumental variables for SLE were selected from another independent GWAS analysis comprising 5201 cases and 6099 controls with European ancestry. Bidirectional two-sample MR was performed using inverse variance weighting, MR-Egger regression, and weighted median methods. A series of sensitivity analyses were conducted to assess the robustness of the ***::The inverse variance weighting showed that IFN-γ had a positive causal association with the risk of SLE (odd ratio [OR] = 1.24, 95% confidence interval [CI]: 1.03–1.47, p = 0.018). IFN-γR2 levels were not associated with SLE risk after adjustment for multiple comparisons (OR= 0.85, 95% CI: 0.73–0.99, p= 0.034). No genetic association was also detected between IFN-γR1 and SLE (OR= 0.97, 95% CI: 0.79–1.19, p= 0.768). Evidence from bidirectional MR did not support reverse causality. The weighted median regression also showed directionally similar estimates. Conclusion::Higher levels of IFN-γ are significantly associated with an increased risk of SLE, providing insights into the pathogenesis of SLE.

关键词： interferon-γ interferon-γreceptor Mendelian randomization risk factor single-nucleotide polymorphism systemic lupus erythematosus

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MAGE-C3 promotes cancer metastasis by inducing epithelial-mesenchymal transition and immunosuppression in esophageal squamous cell carcinoma

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Cancer Communications 2021年第12期41卷 1354-1372页

作者： Qingnan Wu Weimin Zhang Yan Wang Qingjie Min Hongyue Zhang Dezuo Dong Qimin Zhan Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Laboratory of Molecular OncologyPeking University Cancer Hospital&InstituteBeijing 100142P.R.China Shenzhen Bay Laboratory Institute of Cancer ResearchShenzhenGuangdong 518107P.R.China Research Unit of Molecular Cancer Research Chinese Academy of Medical SciencesBeijing 100142P.R.China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of Radiation OncologyPeking University Cancer Hospital&InstituteBeijing 100142P.R.China

Background:Evading immune surveillance is necessary for tumor ***,there is an urgent need to better understand the interaction between metastasis and mechanisms of tumor immune *** this study,we aimed to clarify a novel mechanism that link tumor metastasis and immunosuppression in the development of esophageal squamous cell carcinoma(ESCC).Methods:The expression of melanoma-associated antigen C3(MAGE-C3)was detected using *** assays were used to evaluate the migration and invasion ability of esophageal squamous cell carcinoma(ESCC)*** assays in mice were used to evaluate metastatic ability in ***-mediated cytotoxicity assays were performed to visualize the immune suppression function on tumor *** sequencing was performed to identify differentially expressed genes between MAGE-C3 overexpressing ESCC cells and control *** ontology(GO)enrichment analyses was performed to identify the most altered pathways influenced by *** activation of the interferon-γ(IFN-γ)pathway was analyzed using Western blotting,GAS luciferase reporter assays,immunofluorescence,and flow *** role of MAGE-C3 in the IFN-γpathway was determined by Western blotting and ***,immunohistochemistry and flow cytometry analysis monitored the changes of infiltrated T cell populations in murine lung ***:MAGE-C3 was overexpressed in ESCC *** expression of MAGE-C3 had a significant association with the risk of lymphatic metastasis and poor survival in patients with *** experiments revealed that MAGE-C3 promoted tumor metastasis by activating the epithelial-mesenchymal transition(EMT).MAGE-C3 repressed antitumor immunity and regulated cytokine secretion of T cells,implying an immunosuppressive ***,MAGE-C3 facilitated IFN-γsignaling and upregulated programmed cell death ligand 1(PDŋL1)by binding with IFN-γreceptor 1(IFNGR1)and st

关键词： cancer metastasis epithelial-mesenchymal transition esophageal squamous cell carcinoma immunosuppression interferon-γreceptor interferon-γ melanoma-associated antigen C3

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