Genes and immunity最新文献

Understanding rare genetic variants within the terminal pathway of complement system in preeclampsia.

IF 5 3区医学

Genes and immunity Pub Date : 2024-12-17 DOI: 10.1038/s41435-024-00310-6

A Inkeri Lokki, Michael Triebwasser, Emma Daly, Mitja I Kurki, Markus Perola, Kirsi Auro, Jane E Salmon, Java Anuja, Mark Daly, John P Atkinson, Hannele Laivuori, Seppo Meri

{"title":"Understanding rare genetic variants within the terminal pathway of complement system in preeclampsia.","authors":"A Inkeri Lokki, Michael Triebwasser, Emma Daly, Mitja I Kurki, Markus Perola, Kirsi Auro, Jane E Salmon, Java Anuja, Mark Daly, John P Atkinson, Hannele Laivuori, Seppo Meri","doi":"10.1038/s41435-024-00310-6","DOIUrl":"10.1038/s41435-024-00310-6","url":null,"abstract":"Preeclampsia is a common multifactorial disease of pregnancy. Dysregulation of complement activation is among emerging candidates responsible for disease pathogenesis. In a targeted exomic sequencing study of 609 women with preeclampsia and 2092 non-preeclamptic controls, we identified 14 variants within nine genes coding for components of the membrane attack complex (MAC, C5b-9) that are associated with preeclampsia. We found two rare missense variants in the C5 gene that predispose to preeclampsia (rs200674959: I1296V, OR (CI95) = 24.13 (1.25-467.43), p value = 0.01 and rs147430470: I330T, OR (CI95) = 22.75 (1.17-440.78), p value = 0.01). In addition, one predisposing rare variant and one protective rare variant were discovered in C6 (rs41271067: D396G, OR (CI95) = 2.93 (1.18-7.10), p value = 0.01 and rs114609505: T190I, 0.02 OR (CI95) = 0.47 (0.22-0.92), p value = 0.02). The results suggest that variants in the terminal complement pathway predispose to preeclampsia.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846497","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

FGL1 facilitates rather than suppresses anticancer immunity against microsatellite instable gastric cancer. FGL1促进而非抑制针对微卫星不稳定胃癌的抗癌免疫。

IF 5 3区医学

Genes and immunity Pub Date : 2024-12-13 DOI: 10.1038/s41435-024-00314-2

Zhenyuan Qian, Xufan Cai, Jianzhang Wu, Kun Ke, Zaiyuan Ye, Fang Wu

{"title":"FGL1 facilitates rather than suppresses anticancer immunity against microsatellite instable gastric cancer.","authors":"Zhenyuan Qian, Xufan Cai, Jianzhang Wu, Kun Ke, Zaiyuan Ye, Fang Wu","doi":"10.1038/s41435-024-00314-2","DOIUrl":"https://doi.org/10.1038/s41435-024-00314-2","url":null,"abstract":"Microsatellite instability (MSI) is a phenotype characterized by changes in the sequence length of microsatellites in tumor cells and is closely linked to tumorigenesis and prognosis. Immune checkpoint inhibitors have shown good therapeutic effects in gastric cancer (GC) with MSI-high (MSI-H). However, the role of the novel immune checkpoint fibrinogen-like protein 1 (FGL1) in GC treatment has not been fully investigated. FGL1 expression in GC tissues and the difference in FGL1 immune infiltration between MSI/ microsatellite stability (MSS) patients were analyzed by bioinformatics and were verified in clinical samples. Xenograft models of MSS and MSI GC were constructed in human immune reconstitution mice, and FGL1 expression in tumors was detected. Immunofluorescence and immunohistochemistry were used to assay the infiltration of immune cells in the two types of mice. Cytotoxicity and chemotaxis tests were used to detect the toxicity and chemotaxis of CD8+T cells to GC cells, respectively. The cytokine content was detected by enzyme-linked immunosorbent assay. The therapeutic effects of FGL1 antibody on different types of GC were analyzed by xenograft mouse models. FGL1 exhibited significantly higher expression in GC, and its expression and immune cell infiltration levels were significantly higher in MSI GC than in MSS GC. CD8+T cells were significantly more effective in killing and chemotaxis of MSI GC cells than MSS GC cells. The FGL1 antibody was more effective in treating MSI GC.The novel immunosuppressor FGL1 antibody exerts a good therapeutic influence on MSI GC. These findings provide a basis for the development of drugs targeting FGL1 for MSI GC treatment.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142821801","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: Roles of TULA-family proteins in T cells and autoimmune diseases. 更正：TULA 家族蛋白在 T 细胞和自身免疫性疾病中的作用。

IF 5 3区医学

Genes and immunity Pub Date : 2024-12-09 DOI: 10.1038/s41435-024-00311-5

Hua Wang, Patrick Concannon, Yan Ge

引用次数: 0

GXYLT2: an emerging therapeutic target and predictive biomarker for anti-PD-1 efficacy in clear cell renal cell carcinoma.

IF 5 3区医学

Genes and immunity Pub Date : 2024-12-05 DOI: 10.1038/s41435-024-00312-4

Tuanjie Guo, Jinyuan Chen, Xiangyin Tan, Heting Tang, Xuan Wang, Siteng Chen, Xiang Wang

{"title":"GXYLT2: an emerging therapeutic target and predictive biomarker for anti-PD-1 efficacy in clear cell renal cell carcinoma.","authors":"Tuanjie Guo, Jinyuan Chen, Xiangyin Tan, Heting Tang, Xuan Wang, Siteng Chen, Xiang Wang","doi":"10.1038/s41435-024-00312-4","DOIUrl":"https://doi.org/10.1038/s41435-024-00312-4","url":null,"abstract":"There are studies reporting that glucoside xylosyltransferase 2 (GXYLT2) has a role in promoting tumor progression, but its role in clear cell renal cell carcinoma (ccRCC) remains unclear. In this study, RT-qPCR and western blotting were employed to detect the expression level of GXYLT2. RNA interference assays were used to knock down GXYLT2. CCK-8, wound healing assays, clone formation assays, and Transwell assays were utilized to investigate the function of GXYLT2. Bioinformatics analysis was used to explore the tumor microenvironment and potential biological mechanisms. We found that the expression level of GXYLT2 in ccRCC was higher than that in adjacent normal renal tissues. Patients with high GXYLT2 expression have worse clinical outcomes. Knockdown of GXYLT2 inhibits the proliferation, invasion, migration, and clone formation ability of ccRCC cells. Enrichment analysis uncovered that GXYLT2 participates in Wnt, cell cycle, and actin cytoskeleton regulation signaling pathways. After receiving anti-PD-1 therapy, patients with high GXYLT2 expression had longer progression-free survival compared with those with low GXYLT2 expression. In conclusion, GXYLT2 is a novel potential therapeutic target for ccRCC. Meanwhile, GXYLT2 can be used as a novel marker for predicting immunotherapeutic response.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784959","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 need for Cre-loci controls in conditional mouse experiments: Mrp8-cre transgene predisposes mice to antibody-induced arthritis.

IF 5 3区医学

Genes and immunity Pub Date : 2024-12-04 DOI: 10.1038/s41435-024-00313-3

Zhongwei Xu, Laura Romero-Castillo, Àlex Moreno-Giró, Rajan Kumar Pandey, Rikard Holmdahl

引用次数: 0

The role of NLRP3 and NLRP12 inflammasomes in glioblastoma NLRP3和NLRP12炎症体在胶质母细胞瘤中的作用。

IF 5 3区医学

Genes and immunity Pub Date : 2024-11-27 DOI: 10.1038/s41435-024-00309-z

Sushmita Rajkhowa, Sushmita Jha

{"title":"The role of NLRP3 and NLRP12 inflammasomes in glioblastoma","authors":"Sushmita Rajkhowa, Sushmita Jha","doi":"10.1038/s41435-024-00309-z","DOIUrl":"10.1038/s41435-024-00309-z","url":null,"abstract":"Glioblastoma (GBM) is the deadliest malignant brain tumor, with a survival of less than 14 months after diagnosis. The highly invasive nature of GBM makes total surgical resection challenging, leading to tumor recurrence and declined survival. The heterocellular composition of the GBM reprograms its microenvironment, favoring tumor growth, proliferation, and migration. The innate immune cells in the GBM tumor microenvironment, including microglia, astrocytes, and macrophages, express pattern recognition receptors such as NLRs (Nucleotide-binding domain and leucine-rich repeat-containing) that sense pathogen- and damage-associated molecular patterns initiating inflammation. Upon activation, NLRP3 promotes inflammation by NLRP3 inflammasome formation. Auto-proteolytic cleavage and activation of Caspase-1 within the inflammasome leads to caspase-1-mediated cleavage, activation, and conversion of pro-IL-1ß and pro-IL-18 to IL-1ß and IL-18, leading to pyroptosis. In contrast, NLRP12 downregulates inflammatory responses in microglia and macrophages by regulating the NF-κB pathway. NLRP3 and NLRP12 have been implicated in the disease pathophysiology of several cancers with cell-context-dependent, pro- or anti-tumorigenic roles. In this review, we discuss the current literature on the mechanistic roles of NLRP3 and NLRP12 in GBM and the gaps in the scientific literature in the context of GBM pathophysiology with potential for targeted therapeutics.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"25 6","pages":"541-551"},"PeriodicalIF":5.0,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739252","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

Neoantigen-specific mRNA/DC vaccines for effective anticancer immunotherapy 用于有效抗癌免疫疗法的新抗原特异性 mRNA/DC 疫苗。

IF 5 3区医学

Genes and immunity Pub Date : 2024-11-26 DOI: 10.1038/s41435-024-00305-3

Wenli Zhang, Jiahao Guan, Wenwen Wang, Guo Chen, Li Fan, Zifan Lu

{"title":"Neoantigen-specific mRNA/DC vaccines for effective anticancer immunotherapy","authors":"Wenli Zhang, Jiahao Guan, Wenwen Wang, Guo Chen, Li Fan, Zifan Lu","doi":"10.1038/s41435-024-00305-3","DOIUrl":"10.1038/s41435-024-00305-3","url":null,"abstract":"The development of personalized anticancer vaccines based on neoantigens represents a new direction in cancer immunotherapy. The latest advancement in dendritic cell (DC) tumor vaccine construction involves loading DC with mRNA-encoding neoantigens, which allows for rapid production and is suitable for personalized preparation. Cell-penetrating peptides (CPPs) are emerging as biological delivery systems in which negatively charged nucleic acids can be wound onto the cationic CPP backbone to form nanoscale complexes. This preparation method facilitates standardization. If DC can express and present neoantigen mRNA at high levels, it holds promising application potential. In this study, we developed a neoantigen-mRNA/DC vaccine using candidate neoantigens from mouse colon cancer (MC38) and examined its immune and antitumor effects. The results demonstrated that neoantigen-mRNA/DC vaccines induced strong T cell immune responses and exhibited significant antitumor effects, effectively preventing tumor growth. Our study provides an experimental basis for further optimizing the preparation of DC vaccines and reducing their costs.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"25 6","pages":"514-524"},"PeriodicalIF":5.0,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142727857","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

Roles of TULA-family proteins in T cells and autoimmune diseases. TULA 家族蛋白在 T 细胞和自身免疫性疾病中的作用。

IF 5 3区医学

Genes and immunity Pub Date : 2024-11-18 DOI: 10.1038/s41435-024-00300-8

Hua Wang, Patrick Concannon, Yan Ge

{"title":"Roles of TULA-family proteins in T cells and autoimmune diseases.","authors":"Hua Wang, Patrick Concannon, Yan Ge","doi":"10.1038/s41435-024-00300-8","DOIUrl":"10.1038/s41435-024-00300-8","url":null,"abstract":"The T cell Ubiquitin Ligand (TULA) protein family contains two members, UBASH3A and UBASH3B, that display similarities in protein sequence and domain structure. Both TULA proteins act to repress T cell activation via a combination of overlapping and nonredundant functions. UBASH3B acts mainly as a phosphatase that suppresses proximal T cell receptor (TCR) signaling. In contrast, UBASH3A acts primarily as an adaptor protein, interacting with other proteins (including UBASH3B) in T cells upon TCR stimulation and resulting in downregulation of TCR signaling and NF-κB signaling. Human genetic and functional studies have revealed another notable distinction between UBASH3A and UBASH3B: numerous genome-wide association studies have identified statistically significant associations between genetic variants in and around the UBASH3A gene and at least seven different autoimmune diseases, suggesting a key role of UBASH3A in autoimmunity. However, the evidence for an independent role of UBASH3B in autoimmune disease is limited. This review summarizes key findings regarding the roles of TULA proteins in T cell biology and autoimmunity, highlights the commonalities and differences between UBASH3A and UBASH3B, and speculates on the individual and joint effects of TULA proteins on T cell signaling.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667225","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

Epigenetics behind CD8+ T cell activation and exhaustion CD8+ T 细胞活化和衰竭背后的表观遗传学。

IF 5 3区医学

Genes and immunity Pub Date : 2024-11-14 DOI: 10.1038/s41435-024-00307-1

Hao Zu, Xiaoqin Chen

引用次数: 0

Predictable regulation of gut microbiome in immunotherapeutic efficacy of gastric cancer. 肠道微生物组对胃癌免疫治疗疗效的可预测调节。

IF 5 3区医学

Genes and immunity Pub Date : 2024-11-12 DOI: 10.1038/s41435-024-00306-2

Wei Gao, Xinli Wang, Yi Shi, Guangfeng Wu, Min Zhou, Xiaoyan Lin

{"title":"Predictable regulation of gut microbiome in immunotherapeutic efficacy of gastric cancer.","authors":"Wei Gao, Xinli Wang, Yi Shi, Guangfeng Wu, Min Zhou, Xiaoyan Lin","doi":"10.1038/s41435-024-00306-2","DOIUrl":"https://doi.org/10.1038/s41435-024-00306-2","url":null,"abstract":"Immunotherapy has showcased remarkable progress in the management of gastric cancer (GC), prompting the need to proactively identify and classify patients suitable for immunotherapy. Here, 30 patients were enrolled and stratified into three groups (PR, partial response; SD, stable disease; PD, progressive disease) based on efficacy assessment. 16S rRNA sequencing were performed to analyze the gut microbiome signature of patients at three timepoints. We found that immunotherapy interventions perturbed the gut microbiota of patients. Additionally, although differences at the enterotype level did not distinguish patients' immunotherapy response, we identified 6, 7, and 19 species that were significantly enriched in PR, SD, and PD, respectively. Functional analysis showed that betalain biosynthesis and indole alkaloid biosynthesis were significantly different between the responders and non-responders. Furthermore, machine learning model utilizing only bacterial biomarkers accurately predicted immunotherapy efficacy with an Area Under the Curve (AUC) of 0.941. Notably, Akkermansia muciniphila and Dorea formicigenerans played a significant role in the classification of immunotherapy efficacy. In conclusion, our study reveals that gut microbiome signatures can be utilized as effective biomarkers for predicting the immunotherapy efficacy for GC.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142618624","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