Autoimmunity最新文献

{"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":"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}

{"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":"57 1","pages":"2377138"},"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}

{"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":"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":"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":"57 1","pages":"2387076"},"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}

{"title":"Type B thymomas in patients with myasthenia gravis display a distinctive pattern of αβ TCR and IL-7 receptor α expression on CD4⁺CD8⁺ thymocytes.","authors":"Tianlai Wang, Boyu Wang, Xiaowu Fan, Yixin Cai, Lequn Li, Shengling Fu","doi":"10.1080/08916934.2024.2347379","DOIUrl":"10.1080/08916934.2024.2347379","url":null,"abstract":"<p><p>Thymoma is closely associated with myasthenia gravis (MG). However, due to the heterogeneity of thymoma and the intricate pathogenesis of MG, it remains unclear why some patients with thymoma develop MG and others do not. In this study, we conducted a comparative phenotype analysis of thymocytes in type B thymomas in patients with MG (MG (+) thymomas) and without MG (MG (-) thymomas) <i>via</i> fluorescence-activated cell sorting (FACS). Our results show that the developmental stages defined by the expression of CD3, CD4, and CD8 were largely maintained in both MG (+) and MG (-) thymomas, with CD4⁺CD8⁺ cells constituting the majority of thymocytes in type B thymoma, and no significant difference between this cell population was observed in MG (+) and MG (-) thymomas.We discovered that CD4⁺CD8⁺ thymocytes in MG (+) thymomas expressed low levels of αβ TCR and high levels of IL-7 receptor α (IL-7Rα), whereas in MG (-) thymomas, CD4⁺CD8⁺ thymocytes exhibited the opposite pattern of αβ TCR and IL-7Rα expression. These results suggest that the positive and negative selection processes of CD4⁺CD8⁺ thymocytes might differ between MG (+) thymomas and MG (-) thymomas. The expression of the Helios transcription factor is induced during negative selection and marks a group of T cells that have undergone negative selection and are likely to be deleted due to strong TCR binding with self-peptides/MHC ligands. We observed that the percentage of Helios-positive CD4SP T cells was greater in MG (-) than in MG (+) thymomas. Thus, the differentially regulated selection process of CD4⁺CD8⁺ thymocytes, which involves TCR and IL-7/IL-7Rα signaling, is associated with the presence of MG in type B thymomas.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":"57 1","pages":"2347379"},"PeriodicalIF":3.5,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140897233","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":"Protective effect of quercetin against macrophage-mediated hepatocyte injury via anti-inflammation, anti-apoptosis and inhibition of ferroptosis.","authors":"Yiwen Hou, Chen Chen, Zhurong Li, Jiawen Wu, Sixue Lyu, Di Guo, Ying Liu, Yang Liu, Tiezheng Hou","doi":"10.1080/08916934.2024.2350202","DOIUrl":"https://doi.org/10.1080/08916934.2024.2350202","url":null,"abstract":"<p><p>Yinchenhao Decoction (YCHD) is a classic prescription in traditional Chinese medicine (TCM). It appears to play an important role in anti-inflammation and autoimmunity protection. As one of the key active ingredients in YCHD, quercetin is a novel anti-inflammatory metabolite that exerts protective effects in many autoimmune diseases. However, its role in autoimmune hepatitis (AIH)-related hepatic injury has not been studied. The aim of this study was to reveal the hepatocyte protective mechanism of quercetin. In this study, we used Concanavalin A (Con A) to establish an <i>in vitro</i> hepatocyte injury-associated AIH model. Brl3a hepatocyte injury was induced by the supernatant of J774A.1 cells treated with Con A. We found that quercetin mitigated Con A-induced <i>via</i> macrophage-mediated Brl3a hepatocyte injury. Quercetin administration reduced the levels of alanine transaminase (ALT) and aspartate transaminase (AST) in the supernatant of Con A-treated Brl3a cells and attenuated the infiltration of J774A.1 macrophages induced by Con A. Moreover, quercetin effectively inhibited the expression of proinflammatory cytokines including interleukin-1β (IL-1β) by Con A. Furthermore, quercetin decreased hepatocyte apoptosis and ferroptosis levels in the macrophage-induced hepatocyte injury model. In conclusion, our study indicates that quercetin alleviates macrophage-induced hepatocyte damage by reducing the inflammatory response, apoptosis and ferroptosis. Our work suggests that quercetin might be a potential therapeutic strategy for AIH.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":"57 1","pages":"2350202"},"PeriodicalIF":3.5,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140891326","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":"Increasing expression of dual-specificity phosphatase 12 mitigates oxygen-glucose deprivation/reoxygenation-induced neuronal apoptosis and inflammation through inactivation of the ASK1-JNK/p38 MAPK pathway.","authors":"Jiaxuan He, Siyuan Li, Yunpeng Teng, Hongfei Xiong, Zhuang Wang, Xiaoyao Han, Wei Gong, Ya Gao","doi":"10.1080/08916934.2024.2345919","DOIUrl":"10.1080/08916934.2024.2345919","url":null,"abstract":"<p><p>Dual-specificity phosphatase 12 (DUSP12) is abnormally expressed under various pathological conditions and plays a crucial role in the pathological progression of disorders. However, the role of DUSP12 in cerebral ischaemia/reperfusion injury has not yet been investigated. This study explored the possible link between DUSP12 and cerebral ischaemia/reperfusion injury using an oxygen-glucose deprivation/reoxygenation (OGD/R) model. Marked decreases in DUSP12 levels have been observed in cultured neurons exposed to OGD/R. DUSP12-overexpressed neurons were resistant to OGD/R-induced apoptosis and inflammation, whereas DUSP12-deficient neurons were vulnerable to OGD/R-evoked injuries. Further investigation revealed that DUSP12 overexpression or deficiency affects the phosphorylation of apoptosis signal-regulating kinase 1 (ASK1), c-Jun NH2-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) in neurons under OGD/R conditions. Moreover, blockade of ASK1 diminished the regulatory effect of DUSP12 deficiency on JNK and p38 MAPK activation. In addition, DUSP12-deficiency-elicited effects exacerbating neuronal OGD/R injury were reversed by ASK1 blockade. In summary, DUSP12 protects against neuronal OGD/R injury by reducing apoptosis and inflammation through inactivation of the ASK1-JNK/p38 MAPK pathway. These findings imply a neuroprotective function for DUSP12 in cerebral ischaemia/reperfusion injury.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":"57 1","pages":"2345919"},"PeriodicalIF":3.5,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140891323","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":"A whole blood-based functional assay to characterize immunoglobulin A effector functions","authors":"Alice Bacon, Celia Cartagena García, Karin A. van Schie, René E. M. Toes, Jean-Marc Busnel","doi":"10.1080/08916934.2024.2341629","DOIUrl":"https://doi.org/10.1080/08916934.2024.2341629","url":null,"abstract":"Most investigations on the immune cell-activating potency of IgA used purified total IgA and/or specific isolated cell populations. As IgA2 has been reported to be more pro-inflammatory than IgA1, ...","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":"33 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140560039","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":"Dysregulated CXCL12 expression in osteoblasts promotes B-lymphocytes preferentially homing to the bone marrow in MRL/lpr mice","authors":"Wenjuan Zheng, Yu Tang, Mengwei Cheng, Cui Ma, Xiaoming Fei, Wei Shi","doi":"10.1080/08916934.2024.2319207","DOIUrl":"https://doi.org/10.1080/08916934.2024.2319207","url":null,"abstract":"Objective: Todetect the abnormal distribution of B-lymphocytes between peripheral and bone marrow (BM) compartments and explore the mechanism of abnormal chemotaxis of B-lymphocytes in lupus subjec...","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":"35 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139969333","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}