Journal of Translational Autoimmunity最新文献

{"title":"Vascular injury derived apoptotic exosome-like vesicles trigger autoimmunity","authors":"Sandrine Juillard ,&nbsp;Annie Karakeussian-Rimbaud ,&nbsp;Marie-Hélène Normand ,&nbsp;Julie Turgeon ,&nbsp;Charlotte Veilleux-Trinh ,&nbsp;Alexa C. Robitaille ,&nbsp;Joyce Rauch ,&nbsp;Andrzej Chruscinski ,&nbsp;Nathalie Grandvaux ,&nbsp;Éric Boilard ,&nbsp;Marie-Josée Hébert ,&nbsp;Mélanie Dieudé","doi":"10.1016/j.jtauto.2024.100250","DOIUrl":"10.1016/j.jtauto.2024.100250","url":null,"abstract":"<div><p>According to a central tenet of classical immune theory, a healthy immune system must avoid self-reactive lymphocyte clones but we now know that B cells repertoire exhibit some level of autoreactivity. These autoreactive B cells are thought to rely on self-ligands for their clonal selection and survival. Here, we confirm that healthy mice exhibit self-reactive B cell clones that can be stimulated <em>in vitro</em> by agonists of toll-like receptor (TLR) 1/2, TLR4, TLR7 and TLR9 to secrete anti-LG3/perlecan. LG3/perlecan is an antigen packaged in exosome-like structures released by apoptotic endothelial cells (ApoExos) upon vascular injury. We demonstrate that the injection of ApoExos in healthy animals activates the IL-23/IL-17 pro-inflammatory and autoimmune axis, and produces several autoantibodies, including anti-LG3 autoantibodies and hallmark autoantibodies found in systemic lupus erythematosus. We also identify γδT cells as key mediators of the maturation of ApoExos-induced autoantibodies in healthy mice. Altogether we show that ApoExos released by apoptotic endothelial cells display immune-mediating functions that can stimulate the B cells in the normal repertoire to produce autoantibodies. Our work also identifies TLR activation and γδT cells as important modulators of the humoral autoimmune response induced by ApoExos.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"9 ","pages":"Article 100250"},"PeriodicalIF":4.7,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589909024000200/pdfft?md5=10a63c2cb5c64a890726d7f77c3163c6&pid=1-s2.0-S2589909024000200-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142095934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unlocking therapeutic potential: Targeting lymphocyte activation Gene-3 (LAG-3) with fibrinogen-like protein 1 (FGL1) in systemic lupus erythematosus","authors":"Bing Wang,&nbsp;Biqing Zhang,&nbsp;Min Wu,&nbsp;Ting Xu","doi":"10.1016/j.jtauto.2024.100249","DOIUrl":"10.1016/j.jtauto.2024.100249","url":null,"abstract":"<div><p>Systemic lupus erythematosus (SLE) represents an autoimmune disorder that affects multiple systems. In the treatment of this condition, the focus primarily revolves around inflammation suppression and immunosuppression. Consequently, targeted therapy has emerged as a prevailing approach. Currently, the quest for highly sensitive and specifically effective targets has gained significant momentum in the context of SLE treatment. Lymphocyte activation gene-3 (LAG-3) stands out as a crucial inhibitory receptor that binds to pMHC-II, thereby effectively dampening autoimmune responses. Fibrinogen-like protein 1 (FGL1) serves as the principal immunosuppressive ligand for LAG-3, and their combined action demonstrates a potent immunosuppressive effect. This intricate mechanism paves the way for potential SLE treatment by targeting LAG-3 with FGL1. This work provides a comprehensive summary of LAG-3's role in the pathogenesis of SLE and elucidates the feasibility of leveraging FGL1 as a therapeutic approach for SLE management. It introduces a novel therapeutic target and opens up new avenues of therapeutic consideration in the clinical context of SLE treatment.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"9 ","pages":"Article 100249"},"PeriodicalIF":4.7,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589909024000194/pdfft?md5=9ede3dcb5f11d159f2702ec556ac9231&pid=1-s2.0-S2589909024000194-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141841524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell transcriptomic analysis uncovers heterogeneity in the labial gland microenvironment of primary Sjögren's syndrome","authors":"Jun Huang ,&nbsp;Jia Tang ,&nbsp;Chen Zhang,&nbsp;Tingting Liu,&nbsp;Zhiyong Deng,&nbsp;Lei Liu","doi":"10.1016/j.jtauto.2024.100248","DOIUrl":"10.1016/j.jtauto.2024.100248","url":null,"abstract":"<div><h3>Objective</h3><p>Primary Sjögren's syndrome (pSS) is a systemic autoimmune disorder with an unclear pathogenetic mechanism in the labial gland. This study aims to investigate the cellular and molecular mechanisms contributing to the development of this disease.</p></div><div><h3>Methods</h3><p>Single-cell RNA sequencing (scRNA-seq) was performed on 32,337 cells of labial glands from three pSS patients and three healthy individuals. We analyzed all cell subsets implicated in pSS pathogenesis.</p></div><div><h3>Results</h3><p>Our research revealed diminished differentiation among epithelial cells, concomitant with an enhancement of interferons (IFNs)-mediated signaling pathways. This indicates a cellular functional shift in reaction to inflammatory triggers. Moreover, we observed an augmentation in the population of myofibroblasts and endothelial cells, likely due to the intensified IFNs signaling, suggesting a possible reconfiguration of tissue structure and vascular networks in the impacted regions. Within the immune landscape, there was an apparent increase in immunosuppressive macrophages and dendritic cells (DCs), pointing to an adaptive immune mechanism aimed at modulating inflammation and averting excessive tissue harm. Elevated activation levels of CD4⁺T cells, along with a rise in regulatory T (Treg) cells, were noted, indicating a nuanced immune interplay designed to manage the inflammatory response. In the CD8⁺T cell subsests, we detected a notable increase in cells expressing granzyme K (GZMK), signaling an intensified cytotoxic activity. Additionally, the escalated presence of T cells with high levels of heat shock proteins (HSPs) suggests a cellular stress condition, possibly associated with persistent low-grade inflammation, mirroring the chronic aspect of the condition.</p></div><div><h3>Conclusions</h3><p>Our research identified distinct stromal and immune cell populations linked to pSS, revealing new potential targets for its management. The activation of myeloid, B, and T cells could contribute to pSS pathogenesis, providing important guidance for therapeutic approaches.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"9 ","pages":"Article 100248"},"PeriodicalIF":4.7,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589909024000182/pdfft?md5=28c94a7aa08c4484edc759073e98b10c&pid=1-s2.0-S2589909024000182-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141701616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"To switch or to swap? Evidence from a meta-analysis for the best treatment approach in childhood chronic uveitis resistant to the I anti-TNF","authors":"Ilaria Maccora ,&nbsp;Sara Soldovieri ,&nbsp;Teodoro Oliverio ,&nbsp;Salvatore de Masi ,&nbsp;Edoardo Marrani ,&nbsp;Ilaria Pagnini ,&nbsp;Maria Vincenza Mastrolia ,&nbsp;Gabriele Simonini","doi":"10.1016/j.jtauto.2024.100247","DOIUrl":"https://doi.org/10.1016/j.jtauto.2024.100247","url":null,"abstract":"<div><h3>Objective</h3><p>Since adalimumab approval in childhood chronic non-infectious uveitis (cNIU), the prognosis has been dramatically changed, but the 25 % failed to achieve inactivity. There is not accordance if it is better to switch to another anti-TNF or to swap to another category of biologic. Thus, we aim to summarize evidence regarding the best treatment of cNIU refractory to the first anti-TNF.</p></div><div><h3>Methods</h3><p>A systematic literature review and meta-analysis, according to PRISMA Guidelines, was performed(Jan2000-Aug2023). Studies investigating the efficacy of treatment in cNIU refractory to the first anti-TNF were considered for inclusion. The primary outcome was the improvement of intraocular inflammation according to SUN. A combined estimation of the proportion of children responding to switch or swap and for each drug was performed.</p></div><div><h3>Results</h3><p>23 articles were eligible, reporting 150 children of whom 109 switched anti-TNF (45 adalimumab, 49 infliximab, 9 golimumab) and 41 swapped to another biologics (31 abatacept, 8 tocilizumab and 1 rituximab). The proportion of responding children was 46 %(95 % CI 23-70) for switch and 38 %(95 % CI 8-73) for swap (χ²0.02, p = 0.86). Instead analysing for each drug, the proportion of responding children was the 24 %(95 % CI 2-55) for adalimumab, 43 %(95 % CI 2-80) for abatacept, 79 %(95 % CI 61-93) for infliximab, 56 %(95 % CI 14-95) for golimumab and 96 %(95 % CI 58-100) for tocilizumab. We evaluated a superiority of tocilizumab and infliximab compared to the other drugs(χ² 27.5 p &lt; 0.0001).</p></div><div><h3>Conclusion</h3><p>Although non-conclusive, this meta-analysis suggests that, after the first anti-TNF failure, tocilizumab and infliximab are the best available treatment for the management of cNIU.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"9 ","pages":"Article 100247"},"PeriodicalIF":4.7,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589909024000170/pdfft?md5=0c91f958902d6a7d2c337e34d2d6fdd5&pid=1-s2.0-S2589909024000170-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141487571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Urinary soluble CD163 is useful as “liquid biopsy” marker in lupus nephritis at both diagnosis and follow-up to predict impending flares","authors":"Yves Renaudineau ,&nbsp;Dominique Chauveau ,&nbsp;Stanislas Faguer ,&nbsp;Antoine Huart ,&nbsp;David Ribes ,&nbsp;Gregory Pugnet ,&nbsp;Laurent Sailler ,&nbsp;Thibaut Jamme ,&nbsp;Emmanuel Treiner ,&nbsp;Françoise Fortenfant ,&nbsp;Chloé Bost ,&nbsp;Caroline Carlé ,&nbsp;Julie Belliere","doi":"10.1016/j.jtauto.2024.100244","DOIUrl":"https://doi.org/10.1016/j.jtauto.2024.100244","url":null,"abstract":"<div><p>Lupus nephritis (LN) diagnosis and follow-up requires noninvasive biomarkers. Therefore, the added value of coupling the urinary soluble (s)CD163/creatinuria ratio with serological markers was evaluated in a real-world clinical practice. To this end, a monocentric and retrospective study was conducted in 139 SLE patients with biopsy-proven nephritis having an active LN (LN-A, n = 63 with a positive SLEDAI-renal score) or inactive (n = 76), as well as 98 non-renal SLE patients. The urinary sCD163/creatinuria ratio outperformed serological markers for predicting LN-A (AUC&gt;0.972; p &lt; 10⁻⁴ with a 100 % specificity threshold fixed at 320 ng/mmol), and for monitoring renal activity allowing prediction of impending flares and remissions in follow-up (AUC = 0.789, p &lt; 10⁻⁴). LN-A patients with an elevated spot proteinuria/creatinuria ratio (p = 8 × 10⁻⁶) and sCD163/creatinuria ratio (p = 10⁻³) were at risk for developing end-stage kidney disease but sCD163/creatinuria ratio cannot substitute kidney biopsy to discriminate LN-A from other glomerulonephritis. Among serological markers (n = 14), anti-dsDNA and anti-C1q antibodies (Abs) (AUC&gt;0.750 versus non-LN patients, and AUC&gt;0.640 versus LN-IR patients) best predicted LN-A, and higher levels were retrieved in class III/IV proliferative LN-A. In multivariate logistic regression analysis, the urinary sCD163/creatinuria ratio remained the only statistically significant biomarker to predict LN-A (p &lt; 0.001). In conclusion, and as compared to classical serological markers, the urinary sCD163/creatinuria ratio provides an additional parameter for monitoring LN patients.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"9 ","pages":"Article 100244"},"PeriodicalIF":4.7,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589909024000145/pdfft?md5=5f6c05181e41d12b1f58ed7baadf5037&pid=1-s2.0-S2589909024000145-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141438181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of autoantibodies with the IFN signature and NETosis in patients with systemic lupus erythematosus","authors":"Ellen D. Kaan ,&nbsp;Tammo E. Brunekreef ,&nbsp;Julia Drylewicz ,&nbsp;Lucas L. van den Hoogen ,&nbsp;Maarten van der Linden ,&nbsp;Helen L. Leavis ,&nbsp;Jacob M. van Laar ,&nbsp;Michiel van der Vlist ,&nbsp;Henny G. Otten ,&nbsp;Maarten Limper","doi":"10.1016/j.jtauto.2024.100246","DOIUrl":"https://doi.org/10.1016/j.jtauto.2024.100246","url":null,"abstract":"<div><h3>Objective</h3><p>Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by a variety of disease symptoms and an unpredictable clinical course. To improve treatment outcome, stratification based on immunological manifestations commonly seen in patients with SLE such as autoantibodies, type I interferon (IFN) signature and neutrophil extracellular trap (NET) release may help. It is assumed that there is an association between these immunological phenomena, since NET release induces IFN production and IFN induces autoantibody formation via B-cell activation. Here we studied the association between autoantibodies, the IFN signature, NET release, and clinical manifestations in patients with SLE.</p></div><div><h3>Methods</h3><p>We performed principal component analysis (PCA) and hierarchical clustering of 57 SLE-related autoantibodies in 25 patients with SLE. We correlated each autoantibody to the IFN signature and NET inducing capacity.</p></div><div><h3>Results</h3><p>We observed two distinct clusters: one cluster contained mostly patients with a high IFN signature. Patients in this cluster often present with cutaneous lupus, and have higher anti-dsDNA concentrations. Another cluster contained a mix of patients with a high and low IFN signature. Patients with high and low NET inducing capacity were equally distributed between the clusters. Variance between the clusters is mainly driven by antibodies against histones, RibP2, RibP0, EphB2, RibP1, PCNA, dsDNA, and nucleosome. In addition, we found a trend towards increased concentrations of autoantibodies against EphB2, RibP1, and RNP70 in patients with an IFN signature. We found a negative correlation of NET inducing capacity with anti-FcER (r = −0.530; p = 0.007) and anti-PmScl100 (r = −0.445; p = 0.03).</p></div><div><h3>Conclusion</h3><p>We identified a subgroup of patients with an IFN signature that express increased concentrations of antibodies against DNA and RNA-binding proteins, which can be useful for further patient stratification and a more targeted therapy. We did not find positive associations between autoantibodies and NET inducing capacity. Our study further strengthens the evidence of a correlation between RNA-binding autoantibodies and the IFN signature.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"9 ","pages":"Article 100246"},"PeriodicalIF":4.7,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589909024000169/pdfft?md5=7ab271c4eddb80612212f613a866cdd3&pid=1-s2.0-S2589909024000169-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141444632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PNPLA3 I148 M genetic variant in autoimmune hepatitis characterises advanced disease at diagnosis and reduced survival free of cirrhotic events and liver-related mortality","authors":"Kalliopi Azariadis ,&nbsp;Nikolaos K. Gatselis ,&nbsp;Aggeliki Lyberopoulou ,&nbsp;Pinelopi Arvaniti ,&nbsp;Kalliopi Zachou ,&nbsp;Stella Gabeta ,&nbsp;George N. Dalekos","doi":"10.1016/j.jtauto.2024.100243","DOIUrl":"https://doi.org/10.1016/j.jtauto.2024.100243","url":null,"abstract":"<div><h3>Background</h3><p>Autoimmune hepatitis (AIH) is a relatively rare autoimmune disease with a strong genetic background. The patatin-like phospholipase domain-containing protein 3 (<em>PNPLA3</em>) <em>I148 M</em> (<em>rs7</em>38409 C/G) variant has been associated with hepatic inflammation and fibrosis in chronic hepatic diseases beyond metabolic dysfunction-associated steatotic liver disease (MASLD).</p></div><div><h3>Aim</h3><p>Our aim was to investigate the significance of <em>PNPLA3 I148 M</em> variant in AIH.</p></div><div><h3>Method</h3><p>Two hundred AIH patients, followed in our centre, were evaluated while 100 healthy subjects served as controls. Genotyping was performed with allelic discrimination end-point polymerase chain reaction (PCR).</p></div><div><h3>Results</h3><p>The <em>I148 M</em> variant was present in 95/200 (47.5 %) AIH patients compared to 47/100 (47 %) healthy controls (p = 1.000). Patients with GG/CG genotypes were more likely to present with decompensated cirrhosis at diagnosis (GG/CG 6.3 % vs. CC 1 %, p = 0.039). Comorbidity with cardiometabolic risk factors and concurrence of MASLD was similar across genotypes. Simple steatosis was present in 37/186 (19.9 %) and steatohepatitis in 14/186 (7.5 %) patients with available liver biopsy without correlation with <em>PNPLA3</em> genotype. Fibrosis stage and grade of inflammation were not correlated with any genotype. Response to treatment was also independent of the presence of the <em>I148 M</em> variant, even though a longer time was needed to achieve complete biochemical response in those carrying the GG/CG genotypes (p = 0.07). On Kaplan Meier analysis homozygosity for the G allele corelated with reduced survival free of decompensation (p = 0.006), cirrhotic events (decompensation, liver transplantation, hepatocellular carcinoma; p = 0.001) and liver-related death or liver transplantation (p = 0.011) in treated patients.</p></div><div><h3>Conclusions</h3><p>The <em>PNPLA3 I148 M</em> variant in AIH patients is associated with increased risk of advanced disease at diagnosis and reduced survival free of cirrhotic events and liver-related death or liver transplantation, regardless of the presence of MASLD. This signifies a potential role for the <em>PNPLA3 I148 M</em> variant as a new AIH biomarker allowing to identify patients at increased risk of disease progression.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"9 ","pages":"Article 100243"},"PeriodicalIF":3.9,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589909024000133/pdfft?md5=88106cddb30fad94504e751c77e514d0&pid=1-s2.0-S2589909024000133-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141325237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The new era of immune skin diseases: Exploring advances in basic research and clinical translations","authors":"Bo Zhang ,&nbsp;Xiaole Mei ,&nbsp;Ming Zhao ,&nbsp;Qianjin Lu","doi":"10.1016/j.jtauto.2024.100232","DOIUrl":"10.1016/j.jtauto.2024.100232","url":null,"abstract":"","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"8 ","pages":"Article 100232"},"PeriodicalIF":3.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589909024000029/pdfft?md5=fe40277a1fbc700802b0cd52f1aac353&pid=1-s2.0-S2589909024000029-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139539963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial from the new editor-in-chief","authors":"Yves Renaudineau","doi":"10.1016/j.jtauto.2023.100224","DOIUrl":"10.1016/j.jtauto.2023.100224","url":null,"abstract":"","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"8 ","pages":"Article 100224"},"PeriodicalIF":3.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589909023000370/pdfft?md5=ceca85d18551d4eb2075c6d003907f99&pid=1-s2.0-S2589909023000370-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138608307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Triptolide regulates neutrophil function through the Hippo signaling pathway to alleviate rheumatoid arthritis disease progression","authors":"Pengyuan Liu ,&nbsp;Huiyang Liu ,&nbsp;Yali Sang ,&nbsp;Lingyan Zhu ,&nbsp;Peiyao Zhang ,&nbsp;Chunyan Pang ,&nbsp;Yongfu Wang ,&nbsp;Li Bai","doi":"10.1016/j.jtauto.2024.100242","DOIUrl":"https://doi.org/10.1016/j.jtauto.2024.100242","url":null,"abstract":"<div><p>Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammatory changes in the joints, the etiology of which is unclear. It is now well established that regulated cell death (RCD) and migration of neutrophils play an important role in the pathogenesis of RA. Tripterygium wilfordii Hook.f (TwHF) is a total saponin extracted from the root of Tripterygium wilfordii Hook.f, a plant of the family Wesleyanaceae, which has strong anti-inflammatory and immunomodulatory effects and has been used as a basic drug in the clinical treatment of RA. Despite the good efficacy of TwHF treatment, the mechanism of action of TwHF remains unclear. Several studies have demonstrated that the drug tripterygium glycosides, in which TwHF is the main ingredient, has achieved excellent efficacy in the clinical treatment of RA. Investigations have also found that TwHF can affect cellular RCD, cell migration, cell proliferation, and the apoptosis-related Hippo signaling pathway. In this study, we first analyzed the RCD and migration differences of neutrophils in patients with RA through network pharmacology and transcriptome analysis. Subsequently, we used electron microscopy, immunofluorescence, and other methods to identify the RCD phenotype of neutrophils. In collagen-induced arthritis (CIA) model, we demonstrated that Triptolide (the main active ingredient in TwHF) could alleviate the progression of arthritis by reducing the bone destruction and the infiltration of neutrophils. Furthermore, in vitro experiments showed that Triptolide induced neutrophil apoptosis, inhibited the formation of neutrophil extracellular traps (NETs), and impeded the neutrophil migration process in a Hippo pathway-dependent manner. Taken together, these findings indicate that Triptolide has potential for treating RA and provide theoretical support for the clinical application of TwHF, as a traditional Chinese medicine, in RA.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"8 ","pages":"Article 100242"},"PeriodicalIF":3.9,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589909024000121/pdfft?md5=2ca56dddf1ab03029724871214bfa00d&pid=1-s2.0-S2589909024000121-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140894458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}