Autoimmunity最新文献

{"title":"Transient B-cell depletion and regulatory T-cells mediation in combination with adenovirus mediated IGF-1 prevents and reverses autoimmune diabetes in NOD mice.","authors":"Shujun Ye,&nbsp;Saimei Hua,&nbsp;Meiyang Zhou","doi":"10.1080/08916934.2022.2128782","DOIUrl":"https://doi.org/10.1080/08916934.2022.2128782","url":null,"abstract":"<p><p>Type 1 diabetes (T1D) is one of the T cells mediated autoimmune diseases, although B cells also play an important role in the development. Both T cell and B cell targeted immunotherapies exhibited efficacies in preventing and reversing the T1D. Current study was performed to investigate the protective effects of anti-CD20/CD3 bi-specific antibody (bsAb) in combination with adenovirus mediated mouse insulin-like growth factor 1 (Adv-mIGF-1) gene on T1D in non-obese diabetes (NOD) mice. To simultaneously restore the proportion of Th cells and block the interaction of B cells as well as mediate T cell populations, the NOD model mice were randomly assigned to four groups received the saline, anti-CD20/CD3 bsAb and Adv-mIGF-1 gene alone or combination, respectively. After 16-consecutive weeks intervention, the ELISA, RT-PCR, western blot and histopathological analysis were performed to assess the pancreatic tissues and serum samples to evaluate the treatment effects. Chronic treatment of combination therapy improved T1D morbidity by improving the compartment and function of the CD4⁺Foxp3⁺ Tregs, reversing the secretion of insulin, controlling the blood glucose levels (BGLs) and alleviating insulitis as well as cell apoptosis in the NOD model mice. Moreover, current combination therapy also accelerated the proliferation and differentiation of pancreatic β cells <i>via</i> suppressing the apoptosis-related factors, including caspase-3, caspase-8 and Fas, and activating the Bcl-2-related anti-apoptotic pathway. Furthermore, the cytokeratin-19 (CK-19) and pancreatic duodenal homoplasmic box-1 (PDX-1), as two important stem cell markers of pancreas were both significantly improved by treatment of combination therapy. On conclusions, chronic treatment of anti-CD20/CD3 bsAb in combination with Adv-mIGF-1 gene exerts synergistic protection on T1D in the NOD mice.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33502867","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":"HERC6 is upregulated in peripheral blood mononuclear cells of patients with systemic lupus erythematosus and promotes the disease progression.","authors":"Ling Cao,&nbsp;Hui Zhang,&nbsp;Jin Bai,&nbsp;Tingting Wu,&nbsp;Yingjuan Wang,&nbsp;Ning Wang,&nbsp;Caihong Huang","doi":"10.1080/08916934.2022.2103800","DOIUrl":"https://doi.org/10.1080/08916934.2022.2103800","url":null,"abstract":"<p><p>Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. Peripheral blood mononuclear cells (PBMCs) are any peripheral blood cell with round nuclei, including lymphocytes (T cells, B cells) and monocytes, whose physicochemical properties are randomized by obvious immune changes, and are a potentially effective source of SLE blood test samples and therapeutic targets. This study aimed to explore the upregulation molecules of PBMCs in patients with SLE and to explore their biological role. Homologous to the E6-AP carboxyl terminus (HECT) and regulator of chromosome condensation 1 (RCC1)-like domain (RLD) containing E3 ubiquitin protein ligase family member 6 (HERC6) expression was found significantly upregulated in four Gene Expression Omnibus gene sets. Moreover, HERC6 expression was upregulated in PBMCs from SLE patients compared with that in PBMCs from normal donors. HERC6 was significantly associated with SLE clinical phenotypes such as complement C3 content, erythrocyte sedimentation rate, and SLE disease activity index. <i>In vitro</i>, knockdown of HERC6 inhibited PBMC apoptosis, inflammatory response, and janus kinase (JAK)/signal transducer and activator of transcription (STAT) signalling pathway, while overexpression of HERC6 led to the opposite results. In addition, AG490, a JAK/STAT pathway inhibitor, reversed the promoting effect of HERC6 overexpression on PBMC apoptosis and inflammation. In conclusion, the level of HERC6 in PBMCs in patients with SLE was upregulated. Overexpression of HERC6 promoted PBMC apoptosis and inflammatory response, which was involved in the JAK/STAT pathway.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40554995","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":"microRNA-130b-3p delivery by mesenchymal stem cells-derived exosomes confers protection on acute lung injury.","authors":"Xiaoxia Wang,&nbsp;Jifeng Feng,&nbsp;Huijun Dai,&nbsp;Jianlan Mo,&nbsp;Bijun Luo,&nbsp;Cheng Luo,&nbsp;Weikang Zhang,&nbsp;Linghui Pan","doi":"10.1080/08916934.2022.2094370","DOIUrl":"https://doi.org/10.1080/08916934.2022.2094370","url":null,"abstract":"<p><strong>Objective: </strong>Researchers have investigated miR-130b-3p in lung disease pathology, such as lung fibrosis. The present study was performed to elucidate the miR-130b-3p-involved mechanism in acute lung injury (ALI) through delivery by mesenchymal stem cells-derived exosomes (MSCs-Exo).</p><p><strong>Methods: </strong>ALI mouse models were induced via intratracheal administration of lipopolysaccharide (LPS) and treated with MSCs-Exo. Lung dry-wet (<i>W</i>/<i>D</i>) ratio, inflammatory factors in the bronchoalveolar lavage fluid, pathological damage and apoptosis in the lung tissues were analyzed. Expression levels of miR-130b-3p and TGFBR1 were measured in the mouse lung tissues, and the interaction between miR-130b-3p and TGFBR1 was studied.</p><p><strong>Results: </strong>MSCs-Exo relieved LPS-induced ALI in mice by reducing lung <i>W</i>/<i>D</i> ratio and inflammatory response, and attenuating lung tissue pathological damage and reducing the alveolar cell apoptosis. miR-130b-3p delivery by MSCs-Exo reduced LPS-induced ALI in mice. TGFBR1 was determined to be a downstream target gene of miR-130b-3p. Inhibition of TGFBR1 could remit LPS-induced ALI in mice. The protection mediated by MSCs-Exo carrying miR-130b-3p could be rescued by elevating TGFBR1 expression.</p><p><strong>Conclusion: </strong>miR-130b-3p delivery by MSCs-Exo confers protection on ALI in mice via the downregulation of TGFBR1.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33439872","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":"HSC70 is a novel binding partner involved in the capture of immunoglobulins on B cells in the NOD mouse.","authors":"Emma Renman,&nbsp;Rifat Ekici,&nbsp;Mia Sundström,&nbsp;Kristina Lejon","doi":"10.1080/08916934.2022.2117307","DOIUrl":"https://doi.org/10.1080/08916934.2022.2117307","url":null,"abstract":"<p><p>B cells have been shown to be essential for Type 1 diabetes development in the non-obese diabetic mouse, where their contribution as antigen presenting cells has been emphasised. Other important functions for B cells include surface capture of immunoglobulins and transportation of immune complexes, with subsequent endocytosis, antigen processing and antigen presentation. We have previously demonstrated that NOD B cells capture IgM and IgG immune complexes through an unknown surface molecule. In this study, we revealed the presumptive immunoglobulin-binding molecule to be HSC70. Moreover, we detected increased levels of HSC70 on NOD B cells. HSC70 has been shown to play a role in antigen processing and presentation as well as being important in several autoimmune diseases, including rheumatoid arthritis and systemic lupus erythematosus. Due to its protein stabilising properties, increased HSC70 could contribute to enhanced self-antigen collection and presentation and thereby contribute to the development of Type 1 diabetes.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40366475","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":"Immunoenhancement activity of Bletilla striata polysaccharide through MAPK and NF-κB signalling pathways in vivo and in vitro.","authors":"Xiaofeng Niu,&nbsp;Jiabao Yu,&nbsp;Qiuxia Huang,&nbsp;Jinjin Yu,&nbsp;Yajie Yang,&nbsp;Huixin Song,&nbsp;Yang Liu,&nbsp;Xin Xiao,&nbsp;Langjun Cui,&nbsp;Weifeng Li","doi":"10.1080/08916934.2022.2103801","DOIUrl":"https://doi.org/10.1080/08916934.2022.2103801","url":null,"abstract":"<p><p><i>Bletilla striata</i> (Thunb.) Reichb.f., is a traditional Chinese medicine, and the <i>Bletilla striata</i> polysaccharide (BSP) is one of the principal components extracted from <i>Bletilla striata</i> with various biological activities. Previous studies have shown that many natural polysaccharides have significant immunomodulatory activities. However, as a plant polysaccharide, the research of BSP on immunomodulatory activities is limited. In this study, we aim to investigate the immunomodulatory effect of BSP <i>in vivo</i> and further explore its underlying mechanism <i>in vitro</i>. <i>In vivo</i>, a cyclophosphamide (CTX)-induced immunosuppression mice mode was established by intraperitoneal injection of CTX, and the immune-enhancing effect of BSP (25, 50 and 100 mg/kg) on immunosuppressed mice were evaluated. The result indicated that BSP could significantly improve the immune organ index and the content of immunoglobulin, TNF-α and IL-4 in serum. It was also found that BSP could clearly ameliorate the spleen damage induced by CTX. Meanwhile, the result showed that BSP could not only improve the proliferation of splenocytes, but also activate the lactate dehydrogenase (LDH) and acid phosphatase (ACP) in mouse spleen tissue. <i>In vitro</i>, potential mechanism was further revealed in macrophages. The result supported that BSP could activate macrophages with high phagocytic ability, and induce macrophages to secrete cytokines. Finally, it revealed that activation of NF-κB and MAPK signalling pathway should be the underlying mechanism of the immunoenhancment of BSP.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40549434","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 HOTAIR inhibits the progression of fibroblast-like synoviocytes by sponging miRNA-106b-5p in rheumatoid arthritis.","authors":"Hongxia Qiu,&nbsp;Meixia Liu,&nbsp;Xuefei Shi,&nbsp;Miao Ma,&nbsp;Jing Zhang,&nbsp;Hua Liu","doi":"10.1080/08916934.2022.2126460","DOIUrl":"https://doi.org/10.1080/08916934.2022.2126460","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is a chronic progressive autoimmune disease of unknown etiology. Human fibroblast-like synoviocytes (HFLSs) are the main effector cells for synovial hyperplasia and invasion in RA. Long non-coding RNAs (lncRNAs) play key roles in several autoimmune diseases, including RA. We investigated the effects of lncRNA HOX transcript antisense intergenic RNA (HOTAIR) on the pathological behavior of HFLSs in RA. The microRNAs (miRNAs) with potential binding sites for lncRNA HOTAIR were predicted using Starbase v2.0. TargetScan (http://www.targetscan.org) was used to analyze the potential target genes of miR-106b-5p. The interactions were further verified using a dual-luciferase reporter assay. RNA and protein expression was determined using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting. The proliferation, cell invasion and migration, and cell apoptosis of HFLSs in RA was detected by the 3-(4,5-dimethylthiazol)-2,5-diphenyl-tetrazolium bromide (MTT) assay, transwell assay, and flow cytometry (FCM). The dual luciferase reporter assay confirmed the interactions between lncRNA HOTAIR and miR-106b-5p and between miR-106b-5p and SMAD family member 7 (SMAD7). The qRT-PCR results indicated that the expression of lncRNA HOTAIR was markedly decreased and that of miR-106b-5p was markedly increased in HFLSs of RA. Cell proliferation, invasion, and migration of HFLSs were inhibited by lncRNA HOTAIR upregulation, and the expression of miR-106b-5p was negatively regulated by lncRNA HOTAIR in HFLSs. Apoptosis of HFLS cells was improved by the overexpression of lncRNA HOTAIR. All the effects of lncRNA HOTAIR upregulation on HFLSs were reversed after the overexpression of miR-106b-5p. Smad7 was identified as a target gene of miR-106b-5p, and the effects of downregulation of miR-106b-5p on HFLSs could be abolished by silencing Smad7. We found that lncRNA HOTAIR was significantly downregulated in the HFLSs of patients with RA. Moreover, lncRNA HOTAIR influenced cell growth, migration, invasion, and apoptosis in HFLSs through the miR-106b-5p/Smad7 axis.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40377245","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":"Identified potential biomarkers may predict primary nonresponse to infliximab in patients with ulcerative colitis.","authors":"Jixiang Zhang,&nbsp;Xiaohan Wu,&nbsp;Shuchun Wei,&nbsp;Chuan Liu,&nbsp;Xiaoli Wang,&nbsp;Weiguo Dong","doi":"10.1080/08916934.2022.2103803","DOIUrl":"https://doi.org/10.1080/08916934.2022.2103803","url":null,"abstract":"<p><p>Primary nonresponse to infliximab in patients with ulcerative colitis (UC) is common. However, there are currently no effective biomarkers for this prediction. This study aimed to identify potential predictors for precision anti-tumor necrosis factor-alpha treatment in patients with UC. Four GPL570 datasets (GSE14580, GSE12251, GSE23597, and GSE16879) were included in this study. Sixty-nine differentially expressed genes (DEGs) were identified, while 67 were up-regulated and two were down-regulated by comparing the gene expression in response samples with the nonresponse samples. Gene Ontology analysis showed that DEGs were mostly enriched in neutrophil-mediated immunity, neutrophil activation, neutrophil activation involved in the immune response, neutrophil degranulation, and leukocyte migration. Kyoto Encyclopaedia of Genes and Genomes analysis indicated that these DEGs were mostly enriched in cytokine-cytokine receptor interactions and interleukin (IL)-17 signalling pathways. After protein-protein interaction network analysis, verification by test set, and confirmation of clinical UC samples, S100 calcium-binding protein A8 (S100A8), S100A9, triggering receptor expressed on myeloid cells 1 (TREM1), toll-like receptor 2 (TLR2), IL1B, and formyl peptide receptor 1 (FPR1) were identified as the hub genes. We found that the immune cell composition in the intestinal tissues of UC patients with primary nonresponse included naïve CD4+ T cells, memory resting CD4+ T cells, resting natural killer cells, resting dendritic cells, activating dendritic cells, eosinophils, and neutrophils. Among these, neutrophils showed the most significant differences. In addition, all six potential predictors were significantly associated with the neutrophil count. Our study identified six potential biomarkers, namely S100A8, S100A9, TREM1, TLR2, IL1B, and FPR1, and one type of immune cell, neutrophils, between UC patients with response and primary nonresponse to infliximab. We speculated that changes in the expression of these six potential biomarkers combined with changes in the activity or local quantity of neutrophils might help predict primary nonresponse to infliximab in patients with UC.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40623425","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":"Identification of mite-specific eosinophils in the colon of patients with ulcerative colitis.","authors":"Shu-Wang Peng,&nbsp;Jiang-Ming Sheng,&nbsp;Bai-Sui Feng,&nbsp;Ke-Ping Peng,&nbsp;Gui-Xiang Tian,&nbsp;Cheng-Bai Liang,&nbsp;Ming-Hui Liu,&nbsp;Hai-Qing Xie,&nbsp;Qing Shu,&nbsp;Yan Li,&nbsp;Ping-Chang Yang","doi":"10.1080/08916934.2022.2114467","DOIUrl":"https://doi.org/10.1080/08916934.2022.2114467","url":null,"abstract":"<p><p>The pathogenesis of ulcerative colitis (UC) is unclear. House dust mite (HDM) is associated with immune inflammation in the body. This study is designed to identify the association between HDM and UC clinical symptoms. UC patients (<i>n</i> = 86) and non-UC control (NC) subjects (<i>n</i> = 64) were recruited. Colon lavage fluids (CLF) were collected from HDM skin prick test positive patients during colonoscopy, and analyzed by immunological approaches. HDM was detected in fecal samples, which was positively correlated with UC clinical symptoms. HDM-specific eosinophils and Th2 cells were detected in CLF, which could be specifically activated by exposing to HDM in the culture. Direct exposure to HDM induced eosinophil activation in the colon of UC patients. UC patients displayed elevated levels of Th2 cytokines in the serum. UC clinical symptom scores were positively correlated with serum levels of Th2 cytokines. HDM was detected in UC patients' stools, which was positively correlated with UC clinical symptoms. Direct exposure to HDM could trigger eosinophilic activation of the colon.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40351383","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":"Effect of FcRn antagonism on protective antibodies and to vaccines in IgG-mediated autoimmune diseases pemphigus and generalised myasthenia gravis.","authors":"Jeffrey T Guptill,&nbsp;John W Sleasman,&nbsp;Sophie Steeland,&nbsp;Magdalena Sips,&nbsp;Deborah Gelinas,&nbsp;Hans de Haard,&nbsp;Antoine Azar,&nbsp;Kevin L Winthrop","doi":"10.1080/08916934.2022.2104261","DOIUrl":"https://doi.org/10.1080/08916934.2022.2104261","url":null,"abstract":"<p><p>Antagonism of the neonatal Fc receptor (FcRn) by efgartigimod has been studied in several autoimmune diseases mediated by immunoglobulin G (IgG) as a therapeutic approach to remove pathogenic IgGs. Whereas reduction of pathogenic titres has demonstrated efficacy in multiple autoimmune diseases, reducing total IgG could potentially increase infection risk in patients receiving FcRn antagonists. The objective of this study was to analyse the effect of FcRn antagonism with efgartigimod on existing protective antibody titres and the ability to mount an immune response after vaccine challenge. Serum levels of total IgG and protective antibodies against tetanus toxoid (TT), varicella zoster virus (VZV), and pneumococcal capsular polysaccharide (PCP) were measured in all patients enrolled in an open-label trial of efgartigimod for the treatment of pemphigus. Vaccine specific-responses were assessed by measuring changes in IgG titres in patients with generalised myasthenia gravis (gMG) who were treated with efgartigimod and who received influenza, pneumococcal, or coronavirus disease 2019 (COVID-19) vaccines during participation in the double-blind trial ADAPT or open-label extension, ADAPT+ (<i>n</i> = 17). FcRn antagonism reduced levels of protective anti-TT, anti-VZV, and anti-PCP antibodies and total IgG to a similar extent; anti-TT and anti-VZV titres remained above minimally protective thresholds for the majority of patients, (10/12) 83% and (14/15) 93% respectively. Protective antibodies returned to baseline values upon treatment cessation. Antigen-specific IgG responses to influenza, pneumococcal, and COVID-19 immunisation were detected in patients with gMG who received these vaccines while undergoing therapy with efgartigimod. In conclusion, FcRn antagonism with efgartigimod did not hamper generation of IgG responses but did transiently reduce IgG titres of all specificities.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33445886","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":"Paeoniflorin improves autoimmune myocarditis in young rat by inhibiting CXCR5 to reduce follicular helper T cells.","authors":"Chunxiao Wang,&nbsp;Lanlan Wang,&nbsp;Li Wang","doi":"10.1080/08916934.2022.2128783","DOIUrl":"https://doi.org/10.1080/08916934.2022.2128783","url":null,"abstract":"<p><p>In the current study, we aimed to investigate the effect of paeoniflorin on autoimmune myocarditis. A total of 72 young Lewis rats were randomly divided into control, experimental autoimmune myocarditis (EAM), paeoniflorin low dose (Pae-L 20 mg/kg), paeoniflorin high dose (Pae-H, 40 mg/kg), EAM-NC, CXCR5 siRNA groups, respectively. The levels of TNF-α, IL-6, IFN-γ, and IL-21 were detected. H&E staining was used to investigate the histopathological changes of myocardial tissue. Flow cytometry and immunofluorescence double-labeling assay were used to detect the CD4 and CXCR5. Western blot was employed to investigate the expression of proteins. Pae enhanced the body weight and ameliorated the histopathology and inflammation score of myocardial tissue on day 21 and 35. In the peripheral blood, Pae diminished the proportion of CD4 + CXCR5 + Tfh cells on day 21 and day 35. Furthermore, Pae decreased the expression of CXCR5, CXCL13, programmed cell death-1 (PD-1), phosphorylated p38 (p-p38), phosphorylated ERK1/2 (p-ERK1/2), Bcl-6, and Inducible T cell CO-Stimulator (ICOS) in myocardial tissue on day 35. Our study indicated that paeoniflorin could effectively alleviate autoimmune myocarditis. The mechanism is possibly related to inhibit CXCR5 to reduce Tfh cells <i>via</i> p38 MAPK signaling.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40388491","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}