Genes and immunity最新文献

Correction: Annexin A1 regulates inflammatory-immune response and reduces pancreatic and extra- pancreatic injury during severe acute pancreatitis. 更正：在严重急性胰腺炎中，膜联蛋白A1调节炎症免疫反应并减少胰腺和胰腺外损伤。

IF 4.5 3区医学

Genes and immunity Pub Date : 2025-09-29 DOI: 10.1038/s41435-025-00348-0

Shizhao Lin, Feihong Liang, Changgan Chen, Jiajing Lin, Yuwei Wu, Zelin Hou, Heguang Huang, Haizong Fang, Yu Pan

引用次数: 0

αCGRP deficiency aggravates pulmonary fibrosis by promoting senescence in alveolar type 2 cells. α - cgrp缺乏通过促进肺泡2型细胞衰老而加重肺纤维化。

IF 4.5 3区医学

Genes and immunity Pub Date : 2025-09-29 DOI: 10.1038/s41435-025-00361-3

Xiaoting Lv, Qingquan Chen, Ziying Zhou, Weijing Wu, Xingliang Yu, Yiming Zeng

{"title":"αCGRP deficiency aggravates pulmonary fibrosis by promoting senescence in alveolar type 2 cells.","authors":"Xiaoting Lv, Qingquan Chen, Ziying Zhou, Weijing Wu, Xingliang Yu, Yiming Zeng","doi":"10.1038/s41435-025-00361-3","DOIUrl":"https://doi.org/10.1038/s41435-025-00361-3","url":null,"abstract":"To investigate whether αCGRP (Calca) deficiency exacerbates pulmonary fibrosis (PF) by promoting alveolar type 2 (AT2) cell senescence, we retrospectively analyzed clinical data and lung biopsy samples from PF patients (n = 15). In vivo, lung tissues from Calca-knockout (KO) rats and D-galactose (D-gal)-induced senescence models were analyzed using immunohistochemistry, single-cell RNA sequencing (scRNA-seq), and label-free proteomics. PF patient samples showed low αCGRP expression, AT2 subtype differentiation, and high Calca promoter methylation. In Calca-/- rats, AT2 differentiation and oxidative lipid metabolism were enhanced, with increased senescence gene signatures. scRNA-seq revealed upregulation of linoleic, α-linolenic, and arachidonic acid metabolism, alongside suppression of oxidative stress responses in AT2 of the Calca-/- group. D-gal treatment induced alveolitis, fibrotic changes and AT2 subtype differentiation, and the most severe alveolar inflammation was found in Calca-/-+D-gal rats. Proteomics revealed distinct metabolic pathway alterations between WT + D-gal and Calca-/-+D-gal, and Calca-/- and WT + D-gal rats. Differences in metabolic and PPAR pathways were observed between Calca-/- and Calca-/-+D-gal rats. Additionally, both D-gal treatment and Calca-/- affect oxidative phosphorylation. Overall, αCGRP deficiency disrupts AT2 lipid metabolism, and accelerates AT2 inflammatory senescence, ultimately promoting pulmonary fibrosis.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction: A scan of pleiotropic immune mediated disease genes identifies novel determinants of baseline FVIII inhibitor status in hemophilia A. 更正：多效性免疫介导疾病基因扫描确定了血友病A中FVIII抑制剂基线状态的新决定因素。

IF 4.5 3区医学

Genes and immunity Pub Date : 2025-09-25 DOI: 10.1038/s41435-025-00345-3

Marcio A Almeida, Vincent P Diego, Kevin R Viel, Bernadette W Luu, Karin Haack, Raja Rajalingam, Afshin Ameri, Meera Chitlur, Natalia Rydz, David Lillicrap, Raymond G Watts, Craig M Kessler, Christopher Ramsey, Long V Dinh, Benjamin Kim, Jerry S Powell, Eron G Manusov, Juan M Peralta, Ruayda Bouls, Shirley M Abraham, Yu-Min Shen, Carlos M Murillo, Henry Mead, Paul V Lehmann, Eli J Fine, Miguel A Escobar, Satish Kumar, Barbara A Konkle, Sarah Williams-Blangero, Carol K Kasper, Laura Almasy, Shelley A Cole, John Blangero, Tom E Howard

引用次数: 0

Dexmedetomidine relieves LPS-induced acute lung injury by boosting HIF-1a/ACOD1 driven anti-inflammatory macrophage polarization. 右美托咪定通过增强HIF-1a/ACOD1驱动的抗炎巨噬细胞极化来缓解lps诱导的急性肺损伤。

IF 4.5 3区医学

Genes and immunity Pub Date : 2025-09-24 DOI: 10.1038/s41435-025-00355-1

Ning Zhang, Tangbing Chen, Yintao Chang, Mingzhi Cao, Huan Wang, Chengli Wu, Hong Jiang

{"title":"Dexmedetomidine relieves LPS-induced acute lung injury by boosting HIF-1a/ACOD1 driven anti-inflammatory macrophage polarization.","authors":"Ning Zhang, Tangbing Chen, Yintao Chang, Mingzhi Cao, Huan Wang, Chengli Wu, Hong Jiang","doi":"10.1038/s41435-025-00355-1","DOIUrl":"https://doi.org/10.1038/s41435-025-00355-1","url":null,"abstract":"Acute lung injury (ALI) is a common and life-threatening lung disease. This study investigated the mechanism by which dexmedetomidine (Dex) alleviates lipopolysaccharide (LPS)-induced ALI, focusing on its regulation of macrophage autophagy and polarization. Initially, a mouse model of LPS-induced ALI was pretreated with Dex. Pulmonary function, histopathological changes, apoptosis, macrophage numbers in bronchoalveolar lavage fluid (BALF), M1/M2 macrophage ratios, iNOS/Arg-1/LC3/P62 fluorescence intensity, and autophagy flux were assessed. Subsequently, RAW264.7 macrophages were treated with LPS and Dex, transfected with si-ACOD1 or si-HIF-1α, and co-cultured with mouse pulmonary microvessel endothelial cells (MPMVECs). The results showed that Dex relieved autophagy flux blockage and promoted autophagy in ALI mice. LPS promoted ACOD1 and HIF-1α levels, and Dex further enhanced their levels to boost macrophage autophagy and M2 polarization. ACOD1 was transcriptionally regulated by HIF-1α. Collectively, Dex mitigated LPS-induced MPMVEC injury and ALI by enhancing HIF-1α-mediated ACOD1 transcription, thus promoting macrophage autophagy and M2 polarization.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The epigenomic landscape of bronchial epithelial cells reveals the establishment of trained immunity. 支气管上皮细胞的表观基因组景观揭示了训练免疫的建立。

IF 4.5 3区医学

Genes and immunity Pub Date : 2025-09-24 DOI: 10.1038/s41435-025-00357-z

Jeanne Bigot, Rachel Legendre, Juliette Hamroune, Sébastien Jacques, Mathieu Le Gars, Nicolas Millet, Loïc Guillot, Harriet Corvol, Christophe Hennequin, Juliette Guitard, Jean-Yves Coppée, Viviane Balloy, Claudia Chica

{"title":"The epigenomic landscape of bronchial epithelial cells reveals the establishment of trained immunity.","authors":"Jeanne Bigot, Rachel Legendre, Juliette Hamroune, Sébastien Jacques, Mathieu Le Gars, Nicolas Millet, Loïc Guillot, Harriet Corvol, Christophe Hennequin, Juliette Guitard, Jean-Yves Coppée, Viviane Balloy, Claudia Chica","doi":"10.1038/s41435-025-00357-z","DOIUrl":"https://doi.org/10.1038/s41435-025-00357-z","url":null,"abstract":"Innate immune memory, also called trained immunity, refers to the ability of innate immune cells to gain memory characteristics after transient stimulation, resulting in a nonspecific modified inflammatory response upon secondary remote challenge. Bronchial epithelial cells (BECs) participate in innate immune defence and are the first cells of the lower respiratory tract to encounter inhaled pathogens. We recently showed that BECs are capable of innate immune memory after preexposure to Pseudomonas aeruginosa flagellin through epigenetic mechanisms. In the present study, we investigated such mechanisms through the modification of chromatin architecture induced by flagellin preexposure that results in subsequent changes of gene expression. By conducting an unsupervised approach to jointly analyse chromatin accessibility and gene expression, we mapped the remodelling of the epigenomic and transcriptomic profiles during the establishment of BECs memory. We identified a Memory regulatory profile induced by flagellin exposure. It includes clusters of upregulated genes related to inflammation that are linked to a sustainable gain in chromatin accessibility and with an increased activity of specific transcription factors (TFs) whose binding may drive this process. In summary, we demonstrated that flagellin exposure induced changes in chromatin condensation in BECs, which sustains the reprogramming of transcriptional patterns.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TUG1 targeting enhances anticancer immunity thereby facilitating lenvatinib efficacy in hepatocellular carcinoma. TUG1靶向增强抗癌免疫，从而促进lenvatinib在肝细胞癌中的疗效。

IF 4.5 3区医学

Genes and immunity Pub Date : 2025-09-15 DOI: 10.1038/s41435-025-00358-y

Siyao Che, Longguang He, Qinshou Chen, Yiqiao Mo, Fuliang Li, Junwei Huang, Zikang Ruan

{"title":"TUG1 targeting enhances anticancer immunity thereby facilitating lenvatinib efficacy in hepatocellular carcinoma.","authors":"Siyao Che, Longguang He, Qinshou Chen, Yiqiao Mo, Fuliang Li, Junwei Huang, Zikang Ruan","doi":"10.1038/s41435-025-00358-y","DOIUrl":"https://doi.org/10.1038/s41435-025-00358-y","url":null,"abstract":"Hepatocellular carcinoma (HCC) is a major cause of cancer death globally, with a poor prognosis. The long non-coding RNA TUG1 has been implicated, but its specific role in HCC remains unclear. RT-qPCR was used to evaluate TUG1 and PD-L1 expression, while GEO and TCGA databases were utilized to compare TUG1 levels between HCC patients and healthy controls. In vitro, including CCK8, colony formation, and transwell, assessed cell growth. CD8 + T cell cytotoxicity was evaluated through HCC cells co-culture experiments, and the interaction of miR-377-3p with TUG1 and PD-L1 was examined using dual-luciferase reporter assays. Results indicated that TUG1 was upregulated in HCC, particularly in advanced-stage disease, and PD-L1 expression positively correlated with TUG1 levels. Notably, lenvatinib (LEN) treatment downregulated both TUG1 and PD-L1 in HCC cells, enhancing CD8 + T cell-mediated cytotoxicity. Overexpression of TUG1 diminished the efficacy of LEN, while TUG1 knockdown enhanced it. Mechanistically, TUG1 was found to sponge miR-377-3p, thereby increasing PD-L1 expression. In vivo, TUG1 knockdown combined with LEN treatment significantly reduced tumor growth and PD-L1 expression. In conclusion, TUG1 promotes HCC progression by enhancing PD-L1 through miR-377-3p, with its knockdown enhancing the therapeutic efficacy of LEN, highlighting TUG1's potential as a novel target for HCC treatment.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transcriptomics and eQTLs reveal inflammatory heterogeneity in the duodenal lining in coeliac disease. 转录组学和eqtl揭示了乳糜泻十二指肠内膜的炎症异质性。

IF 4.5 3区医学

Genes and immunity Pub Date : 2025-09-09 DOI: 10.1038/s41435-025-00356-0

Aarón D Ramírez-Sánchez, Stephanie Zühlke, Raúl Aguirre-Gamboa, Martijn Vochteloo, Lude Franke, Knut E A Lundin, Sebo Withoff, Iris H Jonkers

{"title":"Transcriptomics and eQTLs reveal inflammatory heterogeneity in the duodenal lining in coeliac disease.","authors":"Aarón D Ramírez-Sánchez, Stephanie Zühlke, Raúl Aguirre-Gamboa, Martijn Vochteloo, Lude Franke, Knut E A Lundin, Sebo Withoff, Iris H Jonkers","doi":"10.1038/s41435-025-00356-0","DOIUrl":"https://doi.org/10.1038/s41435-025-00356-0","url":null,"abstract":"In coeliac disease (CeD), the epithelial lining (EL) of the small intestine is severely damaged by a complex auto-inflammatory response, leading intraepithelial lymphocytes to attack epithelial cells. To understand the intestinal changes and genetic regulation in CeD, we investigated the heterogeneity in the transcriptomic profile of the duodenal EL using RNA-seq and eQTL analysis on predicted cell types. The study included duodenal biopsies from 82 patients, grouped into controls, gluten-free diet treated CeD and untreated CeD. We identified 1 862 differential expressed genes, which clustered into four sets. Two sets, one upregulated for cell cycle function (n = 366) and one downregulated for digestion, transmembrane transport, and laminin pathways (n = 543), defined three sample groups based on inflammation status: non-inflamed, mild inflammation or severe inflammation. The remaining two sets of genes were enriched for immune (n = 458) and extracellular matrix and barrier functions (n = 495) and were sufficient to classify samples into their disease conditions. Finally, deconvoluting eQTL effects from epithelial and immune cells identified 6 and 15 cell-type-mediated eQTL genes, respectively. In sum, we identified genes expressed in the duodenal EL whose expression reflect heterogeneity in CeD and that may be used as biomarkers to assess CeD condition and its mucosal and immune status.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transcriptional regulation of Ligase IV by an intronic regulatory element directs thymocyte development. 一个内含子调控元件对连接酶IV的转录调控指导胸腺细胞的发育。

IF 4.5 3区医学

Genes and immunity Pub Date : 2025-09-05 DOI: 10.1038/s41435-025-00353-3

Matthew D Estrada, Christopher J Gebhardt, Mariam A Salem, Christina N Rau, Kruthika Sharma, Rebecca A Glynn, Craig H Bassing, Eugene M Oltz, Patrick L Collins

{"title":"Transcriptional regulation of Ligase IV by an intronic regulatory element directs thymocyte development.","authors":"Matthew D Estrada, Christopher J Gebhardt, Mariam A Salem, Christina N Rau, Kruthika Sharma, Rebecca A Glynn, Craig H Bassing, Eugene M Oltz, Patrick L Collins","doi":"10.1038/s41435-025-00353-3","DOIUrl":"10.1038/s41435-025-00353-3","url":null,"abstract":"Double-strand breaks represent the most dangerous form of DNA damage, and in resting cells, these breaks are sealed via the non-homologous end joining (NHEJ) factor Ligase IV (LIG4). Excessive NHEJ may be genotoxic, necessitating multiple mechanisms to control NHEJ activity. However, a clear mechanism of transcriptional control for them has not yet been identified. Here, we examine mechanisms governing Lig4 transcription in mammals, finding that most tissues maintain very low levels of LIG4 production. Select tissues upregulate LIG4, employing different strategies for genomic regulation. In developing lymphocytes, the Lig4 locus is devoid of long-range chromatin contacts; instead, its expression and role in immune development depend upon a promoter-proximal intronic regulatory element. Deletion of the Lig4 intronic regulatory element results in thymocyte-specific loss of Lig4 upregulation, defects in lymphocyte development, and altered antigen receptor rearrangement. Our findings show the NHEJ gene, Lig4, is transcriptionally controlled to support stage-specific function concurrent with programmed DSBs. Moreover, we provide an example of how DNA cis-regulatory elements very close to a promoter can have substantial transcriptional effects.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Discovery of core genes for systemic lupus erythematosus via genome-wide aggregated trans-effects analysis. 通过全基因组聚合反式效应分析发现系统性红斑狼疮的核心基因。

IF 4.5 3区医学

Genes and immunity Pub Date : 2025-09-03 DOI: 10.1038/s41435-025-00352-4

Andrii Iakovliev, Olivia Castellini-Pérez, Buddhiprabha Erabadda, Javier Martín, Guillermo Barturen, Paul M McKeigue, Elena Carnero-Montoro, Marta E Alarcón-Riquelme, Athina Spiliopoulou

{"title":"Discovery of core genes for systemic lupus erythematosus via genome-wide aggregated trans-effects analysis.","authors":"Andrii Iakovliev, Olivia Castellini-Pérez, Buddhiprabha Erabadda, Javier Martín, Guillermo Barturen, Paul M McKeigue, Elena Carnero-Montoro, Marta E Alarcón-Riquelme, Athina Spiliopoulou","doi":"10.1038/s41435-025-00352-4","DOIUrl":"https://doi.org/10.1038/s41435-025-00352-4","url":null,"abstract":"The \"omnigenic\" hypothesis postulates that the polygenic effects of common variants on a typical complex trait coalesce on relatively few core genes through trans-effects on their expression. Our aim was to identify core genes for systemic lupus erythematosus (SLE) by testing for association with genome-wide aggregated trans-effects (GATE) scores for gene expression in a large genetic dataset (5267/4909 SLE cases/controls). SLE was strongly associated with upregulation of expression of eight interferon-stimulated genes driven by shared trans-effects. We estimate that trans-effects on interferon signaling account for 9% of the total genetic effect on SLE risk. Outside this pathway, GATE analysis detected twenty putative core genes for SLE. Direct protein measurements for these genes were strongly associated with SLE in UK Biobank. Two putative core genes (TNFRSF17, TNFRSF13B) encode receptors (BCMA, TACI) expressed on B cells; their ligands (BAFF, APRIL) are targeted by drugs licensed or in development for SLE. Four genes (PDCD1, LAG3, TNFRSF9, CD27) encode receptors that have been characterized as immune checkpoints, and three (CD5L, SIGLEC1, CXCL13) are biomarkers of SLE disease activity. These results provide genetic support for existing drug targets in SLE (interferon signaling, BAFF/APRIL signaling) and identify other possible therapeutic targets including immune checkpoint receptors.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144992228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IRF3 in viral infections: more than just triggering the interferon response. IRF3在病毒感染中的作用：不仅仅是触发干扰素反应。

IF 4.5 3区医学

Genes and immunity Pub Date : 2025-09-02 DOI: 10.1038/s41435-025-00354-2

Marie Bourdon, Caroline Manet, Xavier Montagutelli

引用次数: 0