Pub Date : 2024-12-01Epub Date: 2024-07-21DOI: 10.1080/08916934.2024.2380465
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
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-Faslpr 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.
{"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<sup>lpr</sup> 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":null,"pages":null},"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}
Pub Date : 2024-12-01Epub Date: 2024-02-08DOI: 10.1080/08916934.2024.2310269
Shenming Xu, Dan Wang, Lina Tan, Jianyun Lu
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.
{"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":null,"pages":null},"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}
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-Faslpr/lpr mice and wild-type MRL/MpJ, which were mated with male MRL/MpJ and MRL/MpJ-Faslpr/lpr 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 (Krt15, Slc7a3, Sprr2a3) that significantly regulate pregnancy or immunity. The gene expression of T cell migration-associated chemokines (Ccl5, Cxcl9) 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.
自身免疫性疾病(AID)会改变胎盘免疫环境,导致胎儿死亡。本研究调查了AID对易患AID的MRL/MpJ-Faslpr/lpr小鼠和野生型MRL/MpJ的妊娠和胎盘的影响,野生型MRL/MpJ与雄性MRL/MpJ和MRL/MpJ-Faslpr/lpr在5个月时交配,分别定义为moLpr和moMpJ。在妊娠 15.5 天时评估 AID 指数(脾脏重量和血清自身抗体水平)和生育状况(胎儿数量和大小、形态和胎盘综合基因表达)。moLpr胎盘中的T细胞数量较多,与T辅助细胞2和T滤泡辅助细胞功能相关的基因表达较高,对妊娠或免疫有显著调节作用的基因(Krt15、Slc7a3、Sprr2a3)的表达也发生了改变。在 moLpr 胎盘中,T 细胞迁移相关趋化因子(Ccl5、Cxcl9)的基因表达明显增加,在 moLpr 胎盘中,尤其是在 T 细胞和胎盘成分细胞中分别检测到了 CCL5 和 CXCL9。因此,AID 改变了小鼠的胎盘形态功能和生育能力;然而,在检测的时间点上,生育能力得以维持。这项研究加深了我们对 AID 引起的胎盘改变和妊娠风险的了解。
{"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<sup>lpr/lpr</sup></i> mice and wild-type MRL/MpJ, which were mated with male MRL/MpJ and MRL/MpJ-<i>Fas<sup>lpr/lpr</sup></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":null,"pages":null},"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}
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 via 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.
{"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":null,"pages":null},"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}
Pub Date : 2024-12-01Epub Date: 2024-02-20DOI: 10.1080/08916934.2024.2317190
Ke Liu, Pei Zhang, Ling Zhou, Lin Han, Linhua Zhao, Xiaotong Yu
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.
自身免疫性甲状腺炎(AIT)又称桥本氏甲状腺炎(HT),是一种以甲状腺特异性抗体滴度升高为特征的自身免疫性疾病。AIT 的发病率逐年上升,因此迫切需要建立一种合适的动物模型,以便更好地探索其发病机制和潜在的药物治疗机制。由于缺乏对该疾病的基础研究,建模方法不统一、成功率不明确且参差不齐等问题使得研究人员很难在短期内获得有关 AIT 的有效信息。本报告对目前有关AIT的文献进行了总结和分析,并结合实际可操作性,阐述了不同建模方法使用背后的选择和具体实施过程,以期更好地全面了解自身免疫性甲状腺疾病。
{"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":null,"pages":null},"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}
Pub Date : 2024-12-01Epub Date: 2024-05-21DOI: 10.1080/08916934.2024.2356089
Vasantha L Kolachala, Chungwen Wei, Suresh Venkateswaran, Aisha Latrece Hill, Vivian Warren, Hillary Espinoza, Iñaki Sanz, Nitika A Gupta
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, (n = 12), EA, (n = 11) and controls (n = 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.
{"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<sup>+</sup> IgD<sup>-</sup>/CD27<sup>-</sup> Double Negative (DN<sub>2</sub>) ([CD19+/IgD<sup>-</sup>/CD27<sup>++</sup>CD38<sup>++</sup>) cells. Plasmablasts were significantly higher along with Signalling Lymphocytic activation molecule F7 (SLAMF7). Unswitched memory [CD19+] IgD<sup>+</sup>CD27<sup>+</sup> (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":null,"pages":null},"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}
Pub Date : 2024-12-01Epub Date: 2024-07-14DOI: 10.1080/08916934.2024.2377098
Sabrina Saurin, Myriam Meineck, Paul Claßen, Simone Cosima Boedecker-Lips, Andrea Pautz, Julia Weinmann-Menke
Animal models are an important tool in the research of chronic autoimmune diseases, like systemic lupus erythematosus (SLE). MRL-Faslpr 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-Faslpr mice develop a similar autoimmune disease. Due to the sex bias in human and the delayed disease progression in male MRL-Faslpr mice, the majority of studies have been performed in female mice. To determine the suitability of male MRL-Faslpr 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-Faslpr mice, the use of male mice as part of 3 R-principle and animal welfare must be carefully considered.
动物模型是研究慢性自身免疫性疾病(如系统性红斑狼疮)的重要工具。MRL-Faslpr小鼠是不同狼疮模型中的一种,它们会自发出现类似系统性红斑狼疮的疾病,并伴有自身抗体和免疫复合物沉积,导致不同器官受损。与人类系统性红斑狼疮不同的是,MRL-Faslpr小鼠的雌雄两性都会患上类似的自身免疫性疾病。由于人类存在性别偏见,而雄性MRL-Faslpr小鼠的疾病进展延迟,因此大多数研究都是在雌性小鼠身上进行的。为了确定雄性 MRL-Faslpr 小鼠是否适合用于系统性红斑狼疮研究,特别是在 3 R 原则和动物福利方面,我们对雌雄小鼠的表型、炎症和损伤进行了分析,重点是肾脏和脾脏。雌性小鼠比雄性小鼠更早出现淋巴腺病和皮肤病变。3.5 月龄时,雌性小鼠的肾脏和脾脏比雄性小鼠有更多的免疫细胞浸润。然而,在 5 个月大时,检测到的性别差异要小得多。由于其他研究显示,MRL-Faslpr小鼠的自身免疫性胰腺炎和Sjögren综合症等其他表现也存在雌雄差异,因此必须谨慎考虑使用雄性小鼠作为3R原则和动物福利的一部分。
{"title":"Sex-specific differences in SLE - Significance in the experimental setting of inflammation and kidney damage in MRL-Fas<sup>lpr</sup> 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<sup>lpr</sup> 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<sup>lpr</sup> mice develop a similar autoimmune disease. Due to the sex bias in human and the delayed disease progression in male MRL-Fas<sup>lpr</sup> mice, the majority of studies have been performed in female mice. To determine the suitability of male MRL-Fas<sup>lpr</sup> 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<sup>lpr</sup> 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":null,"pages":null},"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}
Pub Date : 2024-12-01Epub Date: 2024-07-15DOI: 10.1080/08916934.2024.2361749
Chunlei He, Zhaogan Zeng, Yadong Yang, Shanshan Ye, Qiang Wu, Xunzhi Liu, Chenghong Liu, Wanhui Zeng, Sheng Liu
Background: Dysregulated circular RNAs (circRNAs) are involved in osteoarthritis (OA) progression.
Objective: We aimed to explore the effect of hsa_circ_0044719 (circTRIM25) on the ferroptosis of chondrocytes.
Methods: 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.
Results: 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 in vivo.
Conclusion: Silencing of circTRIM25 inhibited ferroptosis of chondrocytes via the miR-138-5p/CREB axis and thus attenuated OA progression.
{"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":null,"pages":null},"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}
Pub Date : 2024-12-01Epub Date: 2024-07-22DOI: 10.1080/08916934.2024.2377138
Faris Mohsin Ali Alabeedi
Keratinocytes in mucosal and skin tissues maintain tissue integrity via desmosomes and desmoglein-3 (Dsg3). Pemphigus Vulgaris (PV) is a life-threatening autoimmune blistering disease characterized by autoantibodies against Dsg3, disrupting desmosomes. Nuclear factor erythroid 2-related factor 2 (Nrf2) regulates oxidative stress responses crucial for skin tissue protection. Although the pathogenesis of PV is known, the detailed molecular events remain unclear. This study investigates changes in Nrf2 expression in keratinocytes following pathogenic anti-Dsg3 antibody AK23 exposure, using dose- and time-dependent studies employing immunofluorescence analysis. N/TERT keratinocytes were cultured in keratinocytes serum-free medium and treated with AK23 at varying doses (5 µg/mL,40µg/mL,75µg/mL) and durations (2, 6, 24 h). Immunofluorescence staining was performed to assess the expression of Nrf2 and Dsg3. All fluorescent images were analyzed using ImageJ software. A dose-dependent increase in Dsg3 was noted following AK23 treatment, while Nrf2 expression and subcellular localization varied. Time-course analyses showed decreased Nrf2 at 24 h and increased Dsg3 levels. Early time-point (2 and 6 h) variations were evident in Nrf2 levels. This study highlights the impact of AK23 on Nrf2 expression, potentially disrupting Nrf2-mediated cytoprotection and implicating oxidative stress (ROS generation) in PV pathogenesis. Further investigation is necessary to validate the findings.
{"title":"Alteration of reactive oxygen species master transcription factor Nrf2 in keratinocytes exposed to monoclonal pathogenic antibody AK23 against desmoglein-3 in pemphigus vulgaris.","authors":"Faris Mohsin Ali Alabeedi","doi":"10.1080/08916934.2024.2377138","DOIUrl":"10.1080/08916934.2024.2377138","url":null,"abstract":"<p><p>Keratinocytes in mucosal and skin tissues maintain tissue integrity <i>via</i> desmosomes and desmoglein-3 (Dsg3). Pemphigus Vulgaris (PV) is a life-threatening autoimmune blistering disease characterized by autoantibodies against Dsg3, disrupting desmosomes. Nuclear factor erythroid 2-related factor 2 (Nrf2) regulates oxidative stress responses crucial for skin tissue protection. Although the pathogenesis of PV is known, the detailed molecular events remain unclear. This study investigates changes in Nrf2 expression in keratinocytes following pathogenic anti-Dsg3 antibody AK23 exposure, using dose- and time-dependent studies employing immunofluorescence analysis. N/TERT keratinocytes were cultured in keratinocytes serum-free medium and treated with AK23 at varying doses (5 µg/mL,40µg/mL,75µg/mL) and durations (2, 6, 24 h). Immunofluorescence staining was performed to assess the expression of Nrf2 and Dsg3. All fluorescent images were analyzed using ImageJ software. A dose-dependent increase in Dsg3 was noted following AK23 treatment, while Nrf2 expression and subcellular localization varied. Time-course analyses showed decreased Nrf2 at 24 h and increased Dsg3 levels. Early time-point (2 and 6 h) variations were evident in Nrf2 levels. This study highlights the impact of AK23 on Nrf2 expression, potentially disrupting Nrf2-mediated cytoprotection and implicating oxidative stress (ROS generation) in PV pathogenesis. Further investigation is necessary to validate the findings.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747352","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}
Objective: This study aims to explore the effect of NONHSAT042241 on the function of rheumatoid arthritis -fibroblast-like synoviocyte (RA-FLS) and the underlying mechanisms.
Methods: RA-FLS was treated with NONHSAT042241 overexpression and NONHSAT042241 knockdown lentiviruses. Cell counting kit-8 (CCK-8) assay, colony formation assay, flow cytometry, Transwell assay, western-blot, ELISA, and qRT-PCR were used to measure the changes of cell proliferation, apoptosis, invasion, secretion of inflammatory cytokines and matrix metalloproteinases (MMPs). Fluorescent in situ hybridization (FISH) assay, RNA pull-down assay, mass spectrometry (MS) and RNA immunoprecipitation (RIP) were used to find the target proteins that bond to NONHSAT042241, and western-blot was used to detect the expression of related proteins of Wnt/β-catenin signaling pathway.
Results: Overexpression of NONHSAT042241 inhibited the proliferation of RA-FLS (p < 0.05), invasion, secretion of pro-inflammatory factors (IL-1and IL-6) and MMPs (MMP-1 and MMP-3) (p < 0.05), and elevated the level of pro-apoptotic factors (Bax and cleaved caspase3), while NONHSAT042241 knockdown had the opposite effect. NONHSAT042241 can directly bind to hnRNP D, and down-regulated the expression of β-catenin (p < 0.05), p-GSK-3β (p < 0.05), Cyclin D1 (p < 0.05), PCNA (p < 0.05), and thus reduced the cell proliferation.
Conclusion: NONHSAT042241 may inhibit FLS-mediated rheumatoid synovial proliferation, inflammation and aggression. The underlying mechanisms may be that NONHSAT042241 inhibits the activity of Wnt/β-catenin signaling.
研究目的本研究旨在探讨NONHSAT042241对类风湿性关节炎纤维母细胞样滑膜细胞(RA-FLS)功能的影响及其内在机制:方法:用NONHSAT042241过表达和NONHSAT042241敲除慢病毒处理RA-FLS。方法:用NONHSAT042241过表达和NONHSAT042241敲除慢病毒处理RA-FLS,采用细胞计数试剂盒-8(CCK-8)检测、集落形成检测、流式细胞术、Transwell检测、Western-blot、ELISA和qRT-PCR检测细胞增殖、凋亡、侵袭、炎性细胞因子和基质金属蛋白酶(MMPs)分泌的变化。荧光原位杂交(FISH)检测、RNA下拉检测、质谱分析(MS)和RNA免疫沉淀(RIP)用于寻找与NONHSAT042241结合的靶蛋白,Western-blot用于检测Wnt/β-catenin信号通路相关蛋白的表达:结果:NONHSAT042241的过表达抑制了RA-FLS的增殖(p p p p p p 结论:NONHSAT042241可能会抑制RA-FLS的增殖:NONHSAT042241可抑制FLS介导的类风湿滑膜增殖、炎症和侵袭。其潜在机制可能是 NONHSAT042241 抑制了 Wnt/β-catenin 信号的活性。
{"title":"LncRNA NONHSAT042241 inhibits rheumatoid synovial proliferation, inflammation and aggression via inactivating WNT/β-catenin signaling pathway.","authors":"Yehua Jin, Cen Chang, Xinpeng Zhou, Runrun Zhang, Ping Jiang, Kai Wei, Linshuai Xu, Yiming Shi, Guizhen Yang, Xinliang Lv, Yuejuan Zheng, Dongyi He","doi":"10.1080/08916934.2024.2387076","DOIUrl":"https://doi.org/10.1080/08916934.2024.2387076","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to explore the effect of NONHSAT042241 on the function of rheumatoid arthritis -fibroblast-like synoviocyte (RA-FLS) and the underlying mechanisms.</p><p><strong>Methods: </strong>RA-FLS was treated with NONHSAT042241 overexpression and NONHSAT042241 knockdown lentiviruses. Cell counting kit-8 (CCK-8) assay, colony formation assay, flow cytometry, Transwell assay, western-blot, ELISA, and qRT-PCR were used to measure the changes of cell proliferation, apoptosis, invasion, secretion of inflammatory cytokines and matrix metalloproteinases (MMPs). Fluorescent <i>in situ</i> hybridization (FISH) assay, RNA pull-down assay, mass spectrometry (MS) and RNA immunoprecipitation (RIP) were used to find the target proteins that bond to NONHSAT042241, and western-blot was used to detect the expression of related proteins of Wnt/β-catenin signaling pathway.</p><p><strong>Results: </strong>Overexpression of NONHSAT042241 inhibited the proliferation of RA-FLS (<i>p</i> < 0.05), invasion, secretion of pro-inflammatory factors (IL-1and IL-6) and MMPs (MMP-1 and MMP-3) (<i>p</i> < 0.05), and elevated the level of pro-apoptotic factors (Bax and cleaved caspase3), while NONHSAT042241 knockdown had the opposite effect. NONHSAT042241 can directly bind to hnRNP D, and down-regulated the expression of β-catenin (<i>p</i> < 0.05), p-GSK-3β (<i>p</i> < 0.05), Cyclin D1 (<i>p</i> < 0.05), PCNA (<i>p</i> < 0.05), and thus reduced the cell proliferation.</p><p><strong>Conclusion: </strong>NONHSAT042241 may inhibit FLS-mediated rheumatoid synovial proliferation, inflammation and aggression. The underlying mechanisms may be that NONHSAT042241 inhibits the activity of Wnt/β-catenin signaling.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124692","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}