Autoimmunity最新文献

{"title":"TMEM164 promotes ferroptosis by selectively mediating ATG5-dependent autophagosome formation to inhibit the progression of LUAD.","authors":"Yongxiang Su, Lintao Li, Junhai Chen, Chao Gao","doi":"10.1080/08916934.2024.2410192","DOIUrl":"10.1080/08916934.2024.2410192","url":null,"abstract":"<p><p>The study focuses on lung adenocarcinoma (LUAD), a predominant type of lung cancer. Despite advancements in diagnostics and molecular therapies, treatment remains challenging due to its low five-year survival rate. This study aims to investigate the role of the transmembrane protein TMEM164 in ferroptosis and anti-tumor immunity in LUAD, and to evaluate its potential as a therapeutic target. Through cellular experiments (such as QPCR, WB, CCK-8, EdU, Transwell, flow cytometry, CO-IP) and animal model experiments (including HE staining and IHC analysis), the relationship between TMEM164 expression and LUAD progression was explored, with particular attention to its mechanisms in ferroptosis and autophagy. The results show that TMEM164 expression is downregulated in LUAD and is associated with poor prognosis. Increasing TMEM164 expression significantly inhibits cell proliferation, migration, and invasion, while promoting an autophagy process dependent on ATG5 for autophagosome formation, thus facilitating ferroptosis. In mouse models, high TMEM164 expression combined with anti-PD-1 antibodies demonstrated synergistic anti-tumor effects. These findings highlight the critical role of TMEM164 in LUAD, suggesting that modulating TMEM164 expression could open new avenues for LUAD treatment.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":"57 1","pages":"2410192"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating interleukin-27 is associated with the risk of chronic periodontitis and allergic rhinitis: A Mendelian randomization analysis.","authors":"Nan Jiang, JingLi Zhao, ChuHuan Zhou, XinRong Nan","doi":"10.1080/08916934.2024.2358070","DOIUrl":"10.1080/08916934.2024.2358070","url":null,"abstract":"<p><strong>Background: </strong>Chronic periodontitis (CP) and allergic rhinitis (AR) have attracted wide attention as global public health problems with high incidence. Recent studies have shown that circulating interleukin-27 (IL-27) is associated with the risk of CP and AR. The aim of this study is to analyze the causal effect between them using Mendelian randomization (MR).</p><p><strong>Methods: </strong>Bidirectional MR analyses were performed with the use of publicly available genome-wide association study (GWAS) data. Summary data on circulating IL-27, CP, and AR published in genome-wide association studies were collected. Instrumental variables (IV) were extracted using assumptions of correlation, independence and exclusivity as criteria. Inverse variance weighting (IVW) was used as the main method, combined with weighted median method (WM) and MR-Egger and other MR Analysis methods for causal inference of exposure and outcome. Cochran's Q and MR-Egger intercept were used for sensitivity analysis.</p><p><strong>Results: </strong>The IVW study showed a causal effect between increased circulating IL-27 levels and increased risk of CP (OR = 1.14, 95%CI = 1.02-1.26, <i>p</i> = .020). Similarly, the increase of circulating IL-27 level had a causal effect on the decreased risk of AR (OR = 0.88, 95%CI = 0.80-0.97, <i>p</i> = .012). In addition, IVW study found that there was a causal between the increased risk of CP and circulating IL-27 level (OR = 1.05, 95%CI = 1.01-1.10, <i>p</i> = .016). However, there was no significant causal relationship between the risk of AR and circulating IL-27 levels (OR = 0.97, 95%CI = 0.91-1.02, <i>p</i> = .209). no significant heterogeneity or horizontal pleiotropy was found in sensitivity analysis.</p><p><strong>Conclusions: </strong>There is a causal effect between circulating IL-27 level and CP, AR, which will help to find new ideas and methods for the diagnosis and treatment of CP and AR.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":"57 1","pages":"2358070"},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141199459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Partial long-term clinical improvement after a BCG challenge in systemic lupus erythematosus-prone mice.","authors":"Valentina P Mora, Francisco B Quero, Tays Troncoso-Bravo, Claudia Orellana, Patricia Pereira, Juan P Mackern-Oberti, Samanta C Funes, Jorge A Soto, Karen Bohmwald, Susan M Bueno, Alexis M Kalergis","doi":"10.1080/08916934.2024.2380465","DOIUrl":"https://doi.org/10.1080/08916934.2024.2380465","url":null,"abstract":"<p><p>Systemic Lupus Erythematosus (SLE) is an autoimmune disorder that causes a breakdown of immune tolerance. Current treatments mainly involve general immunosuppression, increasing the risk of infections. On the other hand, Bacillus Calmette-Guérin (BCG) has been investigated as a potential therapy for autoimmune diseases in recent years, prompting an ongoing investigation. This study aimed to evaluate the effect of BCG vaccination on early and late clinical presentation of SLE in a murine disease model. MRL/MPJ-Fas^lpr mice were immunized with BCG or treated with PBS as a control. The progress of the disease was evaluated at 27 days post-immunization (dpi) (early) and 56 dpi (late). Clinical parameters and proteinuria were monitored. Blood samples were collected for measurement of antinuclear antibodies (ANAs), anti-double-stranded DNA (anti-dsDNA), and cytokine determination was performed using ELISA. Samples collected from mice were analyzed by flow cytometry and histopathology. We observed a clinical improvement in BCG-treated mice, reduced proteinuria in the latter stages of the disease, and decreased TNF-α. However, BCG did not elicit significant changes in ANAs, anti-dsDNA, histopathological scores, or immune cell infiltration. BCG was only partially beneficial in an SLE mouse model, and further research is needed to determine whether the immunity induced by this vaccine can counteract lupus's autoimmune response.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":"57 1","pages":"2380465"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of NLRP3 inflammasome in type 2 inflammation related diseases.","authors":"Shenming Xu, Dan Wang, Lina Tan, Jianyun Lu","doi":"10.1080/08916934.2024.2310269","DOIUrl":"10.1080/08916934.2024.2310269","url":null,"abstract":"<p><p>Type 2 inflammation related diseases, such as atopic dermatitis, asthma, and allergic rhinitis, are diverse and affect multiple systems in the human body. It is common for individuals to have multiple co-existing type 2 inflammation related diseases, which can impose a significant financial and living burden on patients. However, the exact pathogenesis of these diseases is still unclear. The NLRP3 inflammasome is a protein complex composed of the NLRP3 protein, ASC, and Caspase-1, and is activated through various mechanisms, including the NF-κB pathway, ion channels, and lysosomal damage. The NLRP3 inflammasome plays a role in the immune response to pathogens and cellular damage. Recent studies have indicated a strong correlation between the abnormal activation of NLRP3 inflammasome and the onset of type 2 inflammation. Additionally, it has been demonstrated that suppressing NLRP3 expression effectively diminishes the inflammatory response, highlighting its promising therapeutic applications. Therefore, this article reviews the role of NLRP3 inflammasome in the development and therapy of multiple type 2 inflammation related diseases.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":"57 1","pages":"2310269"},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139705974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of autoimmune abnormalities on fertility and placental morphology in mice.","authors":"Risa Yamanaka, Osamu Ichii, Teppei Nakamura, Yuki Otani, Takashi Namaba, Yasuhiro Kon","doi":"10.1080/08916934.2024.2319209","DOIUrl":"10.1080/08916934.2024.2319209","url":null,"abstract":"<p><p>Autoimmune diseases (AIDs) alter the placental immune environment leading to fetal loss. This study investigated the effects of AIDs on pregnancy and the placenta in AID-prone MRL/MpJ-<i>Fas^lpr/lpr</i> mice and wild-type MRL/MpJ, which were mated with male MRL/MpJ and MRL/MpJ-<i>Fas^lpr/lpr</i> at five months and defined as moLpr and moMpJ, respectively. AID indices (spleen weight and serum autoantibody levels) and fertility status (number and size of fetuses, morphology, and comprehensive gene expression of placentas) were evaluated on gestational day 15.5. Both strains showed equivalent fertility, but moLpr showed lighter placentas and fetuses than moMpJ, and decreased fertility with AID severity. moLpr placentas had a higher number of T cells, higher expression of genes associated with T helper 2 and T follicular helper functions, and altered expression of genes (<i>Krt15, Slc7a3</i>, <i>Sprr2a3</i>) that significantly regulate pregnancy or immunity. The gene expression of T cell migration-associated chemokines (<i>Ccl5</i>, <i>Cxcl9</i>) was significantly increased in moLpr placentas, and CCL5 and CXCL9 were detected in moLpr placentas, particularly in T cells and placenta-component cells, respectively. Thus, AID altered placental morphofunction and fertility in mice; however, fertility was maintained at the examined time points. This study enhances our understanding of placental alterations and gestational risk due to AIDs.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":"57 1","pages":"2319209"},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139929813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KISS-1 knockdown inhibits cell growth, migration, and invasion in HTR-8/SVneo cells by regulating the GRP54-mediated PI3K/AKT signaling pathway.","authors":"Lingna Chen, Yuying Ruan, Liping Ni, Guiting Wang, Yajuan Gao, Jindi Zhang, Dingheng Li, Haiou Xu","doi":"10.1080/08916934.2023.2297564","DOIUrl":"10.1080/08916934.2023.2297564","url":null,"abstract":"<p><p>Recurrent spontaneous abortions (RSA) affect reproductive health and increase the risk of subsequent abortions. To investigate the role of KISS-1/GPR-54 signaling in RSA progression. Villus tissue was collected from RSA patients, and human trophoblastic HTR-8/SVneo cells were used. KISS-1 and GRP54 levels were detected using RT-qPCR and immunohistochemistry. Western blotting was performed to analyze ZO-1 and ZEB1 levels. Cell proliferation was determined <i>via</i> CCK-8 and cell clone formation assays. Transwell assays were performed to assess cell migration and invasion abilities. KISS-1 was down-regulated in the villus tissues of RSA patients. KISS-1 overexpression dramatically inhibited trophoblast proliferation, migration, and invasion. Mechanistically, ZEB1 expression was down-regulated, whereas ZO-1 expression was up-regulated, after KISS-1 overexpression. GPR54 silencing neutralized the effect of KISS-1 in HTR-8/SVneo cells. Additionally, KISS-1 overexpression inactivated the PI3K/AKT signaling pathway through GRP54. The KISS-1/GPR-54 signaling axis regulates RSA progression by regulating the PI3K/AKT signaling pathway.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":"57 1","pages":"2297564"},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139058115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research progress in the construction of animal models of autoimmune thyroiditis.","authors":"Ke Liu, Pei Zhang, Ling Zhou, Lin Han, Linhua Zhao, Xiaotong Yu","doi":"10.1080/08916934.2024.2317190","DOIUrl":"10.1080/08916934.2024.2317190","url":null,"abstract":"<p><p>Autoimmune thyroiditis (AIT), also known as Hashimoto's thyroiditis (HT), is an autoimmune disease that is characterised by elevated thyroid-specific antibody titres. The incidence of AIT is increasing year over year, making it urgent to establish a suitable animal model for this condition, in order to better explore its pathogenesis and potential pharmaceutical mechanisms for treatment. Owing to a lack of basic research on this disease, problems such as disparate modelling methods with unclear and varying success rates make it difficult for researchers to obtain effective information on AIT in the short term. This report summarises and analyzes the current literature on AIT and combines actual operability to explain the selection and specific implementation processes behind the uses of different modelling approaches, to provide a better overall understanding of autoimmune thyroid diseases.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":"57 1","pages":"2317190"},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139911953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased IgD and CD27 Double Negative (DN) B cell population in pediatric onset autoimmune hepatitis.","authors":"Vasantha L Kolachala, Chungwen Wei, Suresh Venkateswaran, Aisha Latrece Hill, Vivian Warren, Hillary Espinoza, Iñaki Sanz, Nitika A Gupta","doi":"10.1080/08916934.2024.2356089","DOIUrl":"10.1080/08916934.2024.2356089","url":null,"abstract":"<p><p>Autoimmune hepatitis (AIH) is a chronic, inflammatory liver disease of unknown aetiology which requires lifelong immunosuppression. Most therapeutic and outcome studies of AIH have been conducted predominantly in Caucasian (European Ancestry, EA) cohorts, with the exclusion of African American (AA) patients due to inadequate sample size. It is known that AA patients have a severe phenotype of autoimmune diseases and demonstrate a poor response to conventional medical therapy. Understanding cellular and molecular pathways which determine AIH severity and progression in AA patients is likely to lead to the discovery of novel, personalised and better tolerated therapies. The aim of the study is to determine the distinct effector B cell phenotypes which contribute to disease severity and progression of AIH in AA children as compared to their EA cohorts. PBMCs were isolated from blood samples collected from patients visiting Children's Healthcare of Atlanta (CHOA) and were grouped into AA, (<i>n</i> = 12), EA, (<i>n</i> = 11) and controls (<i>n</i> = 12) and were processed for flow cytometry. Markers of B cell development, maturation and activation were assessed namely CD19, CD21, IgD, CD27, CD38, CD11c, CD24, CD138. AA children with AIH demonstrated an expansion of CD19 + ve, Activated Naïve (aN), (CD19⁺ IgD^-/CD27^- Double Negative (DN₂) ([CD19+/IgD^-/CD27⁺⁺CD38⁺⁺) cells. Plasmablasts were significantly higher along with Signalling Lymphocytic activation molecule F7 (SLAMF7). Unswitched memory [CD19+] IgD⁺CD27⁺ (USM) B cells were significantly contracted in AA patients with AIH. B cell phenotyping reveals a distinct profile in AA AIH patients with a major skewing towards the expansion of effector pathways which have been previously characterised in severe SLE in AA patients. These results suggest that the quantification and therapeutic target of B cell pathway could contribute substantially to the clinical approach to AIH especially in the AA population.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":"57 1","pages":"2356089"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141070579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silencing of CircTRIM25/miR-138-5p/CREB1 axis promotes chondrogenesis in osteoarthritis.","authors":"Chunlei He, Zhaogan Zeng, Yadong Yang, Shanshan Ye, Qiang Wu, Xunzhi Liu, Chenghong Liu, Wanhui Zeng, Sheng Liu","doi":"10.1080/08916934.2024.2361749","DOIUrl":"10.1080/08916934.2024.2361749","url":null,"abstract":"<p><strong>Background: </strong>Dysregulated circular RNAs (circRNAs) are involved in osteoarthritis (OA) progression.</p><p><strong>Objective: </strong>We aimed to explore the effect of hsa_circ_0044719 (circTRIM25) on the ferroptosis of chondrocytes.</p><p><strong>Methods: </strong>Chondrocytes were treated with interleukin (IL)-1β to generate cell model. Cellular behaviours were measured using cell counting kit-8, enzyme-linked immunosorbent assay, relevant kits, propidium iodide staining, and immunofluorescence assay. Quantitative real-time polymerase chain reaction was performed to examine the expression of circTRIM25, miR-138-5p, and cAMP responsive element binding protein 1 (CREB1), and their interactions were assessed using luciferase reporter analysis and RNA pull-down assay.</p><p><strong>Results: </strong>CircTRIM25 was upregulated in OA tissues and IL-1β-stimulated chondrocytes. Knockdown of circTRIM25 facilitated the viability and suppressed ferroptosis and inflammation of IL-1β-induced cells. CircTRIM25 served as a sponge of miR-138-5p, which directly targets CREB1. Downregulation of miR-138-5p abrogated the effect induced by knockdown of circTRIM25. Furthermore, enforced CREB1 reversed the miR-138-5p induced effect. Moreover, knockdown of circTRIM25 attenuated cartilage injury <i>in vivo</i>.</p><p><strong>Conclusion: </strong>Silencing of circTRIM25 inhibited ferroptosis of chondrocytes <i>via</i> the miR-138-5p/CREB axis and thus attenuated OA progression.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":"57 1","pages":"2361749"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141615870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-specific differences in SLE - Significance in the experimental setting of inflammation and kidney damage in MRL-Fas^lpr mice.","authors":"Sabrina Saurin, Myriam Meineck, Paul Claßen, Simone Cosima Boedecker-Lips, Andrea Pautz, Julia Weinmann-Menke","doi":"10.1080/08916934.2024.2377098","DOIUrl":"https://doi.org/10.1080/08916934.2024.2377098","url":null,"abstract":"<p><p>Animal models are an important tool in the research of chronic autoimmune diseases, like systemic lupus erythematosus (SLE). MRL-Fas^lpr mice are one of different lupus models that develop spontaneously an SLE-like disease with autoantibodies and immune complex deposition that leads into damage of different organs. In contrast to human SLE, both sexes of MRL-Fas^lpr mice develop a similar autoimmune disease. Due to the sex bias in human and the delayed disease progression in male MRL-Fas^lpr mice, the majority of studies have been performed in female mice. To determine the suitability of male MRL-Fas^lpr mice for SLE research, especially with regard to the 3 R-principle and animal welfare, analyses of phenotype, inflammation and damage with focus on kidney and spleen were performed in mice of both sexes. Female mice developed lymphadenopathy and skin lesions earlier as males. At an age of 3.5 month, more immune cells infiltrated kidney and spleen in females compared to males. At the age of 5 months, however, substantially less sex-specific differences were detected. Since other studies have shown differences between both sexes on other manifestations like autoimmune pancreatitis and Sjögren syndrome in MRL-Fas^lpr mice, the use of male mice as part of 3 R-principle and animal welfare must be carefully considered.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":"57 1","pages":"2377098"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141615869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}