ImmunobiologyPub Date : 2024-02-15DOI: 10.1016/j.imbio.2024.152792
Chenhao Xing , Lijing Huo , Hongyue Tang , Yamin Lu , Guangxia Liu , Fang Chen , Zhan Hou
{"title":"The predictive value of miR-377 and phospholipase A2 in the early diagnosis of diabetic kidney disease and their relationship with inflammatory factors","authors":"Chenhao Xing , Lijing Huo , Hongyue Tang , Yamin Lu , Guangxia Liu , Fang Chen , Zhan Hou","doi":"10.1016/j.imbio.2024.152792","DOIUrl":"10.1016/j.imbio.2024.152792","url":null,"abstract":"<div><h3>Objective</h3><p>The value of novel biomarkers for DKD has received increasing attention, and there is an urgent need for novel biomarkers with sensitivity, specificity and ability to detect kidney damage.miR-377 regulates many basic biological processes, plays a key role in tumor cell proliferation, migration and inflammation, and can also increase the expression of matrix proteins and fibronectin, leading to renal tubulointerstitial inflammation and renal fibrosis. Lipoprotein-associated phospholipase A2, as an inflammatory marker, is involved in the pathological process of microalbuminuria production and renal function decline, and is a predictive factor of microalbuminuria production and renal function decline, and can be used as an indicator to evaluate the progression of DKD.The aim of this study was to investigate the effects of miR-377 and phospholipase A2 on the development of diabetic kidney disease through regulation of inflammatory factors and the mechanism of action.<strong>Methods:</strong> 80 diabetic patients were divided into two groups according to urinary albumin-to-creatinine ratio (UACR): diabetic normal proteinuria group (n = 42) and diabetic proteinuria group (n = 38). Forty-three healthy people were selected as the normal control group. The serum levels of TGF-β, IL-6, and IL-18 were measured by ELISA, miR-377 was detected by qPCR, and the serum levels of phospholipase A2 were detected by electrochemiluminescence. Analyze the correlation of study group indicators, ROC curve was used to evaluate the diagnostic efficacy of miR-377 and phospholipase A2 in diabetic kidney disease. <strong>Results:</strong> The average levels of serum TGF-β, IL-6, IL-18, miR-377 and phospholipase A2 in diabetic proteinuria group were significantly higher than those in normal control group and diabetic proteinuria normal group(P < 0.05). miR-377, phospholipase A2 were significantly correlated with inflammatory factors such as glomerular filtration rate and TGF-β. miR-377 and phospholipase A2 are independent predictors of diabetic kidney disease. The area under the curve of miR-377 and phospholipase A2 in the normal diabetic proteinuria group and the diabetic proteinuria group were 0.731 and 0.744, respectively. <strong>Conclusion:</strong> miR-377 and phospholipase A2 have good diagnostic efficiency for the early diagnosis of diabetic kidney disease. They can be used as early biomarkers.miR-377 and phospholipase A2 were positively correlated with inflammatory factors and involved in the occurrence and development of diabetic kidney disease.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 2","pages":"Article 152792"},"PeriodicalIF":2.8,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S017129852400010X/pdfft?md5=6983194224f2bce5aa03350613e28105&pid=1-s2.0-S017129852400010X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139879127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ImmunobiologyPub Date : 2024-02-14DOI: 10.1016/j.imbio.2024.152791
{"title":"Identification and validation of potential biomarkers related to oxidative stress in idiopathic pulmonary fibrosis","authors":"","doi":"10.1016/j.imbio.2024.152791","DOIUrl":"10.1016/j.imbio.2024.152791","url":null,"abstract":"<div><p>Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic interstitial pneumonia with a poor prognosis and a pathogenesis that has not been fully elucidated. Oxidative stress is closely associated with IPF. In this research, we aimed to identify reliable diagnostic biomarkers associated with the oxidative stress through bioinformatics techniques. The gene expression profile data from the GSE70866 dataset was retrieved from the gene expression omnibus (GEO) database. We extracted 437 oxidative stress-related genes (ORGs) from gene set enrichment analysis (GSEA). The GSE141939 dataset was used for single-cell RNA-seq analysis to identify the expression of diagnostic genes in different cell clusters. A total of 10 differentially expressed oxidative stress-related genes (DE-ORGs) were screened. Subsequently, SOD3, CD36, ACOX2, RBM11, CYP1B1, SNCA, and MPO from the 10 DE-ORGs were identified as diagnostic genes based on random forest algorithm with randomized least absolute shrinkage and selection operator (LASSO) regression. A nomogram was constructed to evaluate the risk of disease. The decision curve analysis (DCA) and clinical impact curves indicated that the nomogram based on these seven biomarkers had extraordinary predictive power. Immune cell infiltration analysis results revealed that DE-ORGs were closely related to various immune cells, especially CYP1B1 was in positive correlation with monocytes and negative correlation with macrophages M1. Single-cell RNA-seq analysis showed that CYP1B1 was mainly associated with macrophages, and SNCA was mainly associated with basal cells. CYP1B1 and SNCA were diagnostic genes associated with oxidative stress in IPF.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 5","pages":"Article 152791"},"PeriodicalIF":2.5,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000093/pdfft?md5=31602a8da5c42ec542df4cda524036fa&pid=1-s2.0-S0171298524000093-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139879552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Transmission patterns of C1-INH deficiency hereditary angioedema favors a wild-type male offspring: Our experience at Chandigarh, India","authors":"Sanghamitra Machhua , Ankur Kumar Jindal , Suprit Basu , Isheeta Jangra , Prabal Barman , Rahul Tyagi , Archan Sil , Reva Tyagi , Anit Kaur , Sanchi Chawla , Sendhil M. Kumaran , Sunil Dogra , Manpreet Dhaliwal , Saniya Sharma , Amit Rawat , Surjit Singh","doi":"10.1016/j.imbio.2024.152790","DOIUrl":"https://doi.org/10.1016/j.imbio.2024.152790","url":null,"abstract":"<div><h3>Background</h3><p>Deficiency of C1-inhibitor (C1-INH) protein, caused by pathogenic variants in the Serpin family G member 1 (<em>SERPING1</em>) gene, is the commonest pathophysiological abnormality (in ∼95 % cases) in patients with hereditary angioedema (HAE). C1-INH protein provides negative control over kallikrein–kinin system (KKS). Although the inheritance of the HAE-C1-INH is autosomal dominant, female predominance has often been observed in patients with HAE.</p></div><div><h3>Objective</h3><p>To analyze the risk of transmission of <em>SERPING1</em> gene variant from father or mother to their offspring.</p></div><div><h3>Methods</h3><p>Pedigree charts of 42 families with a confirmed diagnosis of HAE-C1-INH and a pathogenic variant in the <em>SERPING1</em> gene were analysed. Patients with HAE who had had at least one child were included for analyses to assess the risk of transmission from the father or mother to their offspring.</p></div><div><h3>Results</h3><p>Overall, 49 % (189/385) of all offspring inherited the genetic defect. In the subgroup analyses, 54.8 % (90/164) female offspring and 44.8 % (99/221; p < 0.02) male offspring inherited the genetic defect. Inheritance of the genetic defect was significantly lower in male offspring. Fathers with <em>SERPING1</em> gene variant had a statistically significant skewed transmission of the wild type to the male offspring as compared to the variant (57.8 % wild type vs. 42.1 % variant; p < 0.02), whereas no statistically significant difference was found when a father transmitted the variant to a female offspring. Mothers with <em>SERPING1</em> gene variant had no statistically significant difference in variant transmission to male or female offsprings.</p></div><div><h3>Conclusion</h3><p>Results of the study suggest that the transmission pattern of <em>SERPING1</em> gene variant favours the transmission of wild-type alleles in males, especially when the father is the carrier; hence, overall, fewer males and more female offspring inherited the variant. This could be because of a selection of wild-type male sperms during spermatogenesis, as the KLK system has been reported to play a crucial role in the regulation of spermatogenesis. Although, a similar pattern was observed in the maternal transmission of the <em>SERPING1</em> gene variant; the difference was not statistically significant, likely because of a small sample size.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 2","pages":"Article 152790"},"PeriodicalIF":2.8,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000081/pdfft?md5=254aa6bda197b894d8235c2c5f28d66d&pid=1-s2.0-S0171298524000081-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139714417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ImmunobiologyPub Date : 2024-01-28DOI: 10.1016/j.imbio.2024.152788
Wanlu Su , Yaqi Yin , Yu Cheng , Songyan Yu , Ruofan Hu , Haixia Zhang , Jia Hu , Rui Ren , Yue Zhang , Jian Zhao , Anning Wang , Zhaohui Lyu , Yiming Mu , Jieqing Gao
{"title":"The phenotype and related gene expressions of macrophages in adipose tissue of T2D mice following MSCs infusion","authors":"Wanlu Su , Yaqi Yin , Yu Cheng , Songyan Yu , Ruofan Hu , Haixia Zhang , Jia Hu , Rui Ren , Yue Zhang , Jian Zhao , Anning Wang , Zhaohui Lyu , Yiming Mu , Jieqing Gao","doi":"10.1016/j.imbio.2024.152788","DOIUrl":"10.1016/j.imbio.2024.152788","url":null,"abstract":"<div><h3>Background</h3><p>Infusion of mesenchymal stem cells (MSCs) induces polarization of M2 macrophages in adipose tissue of type 2 diabetes (T2D) mice. Studies have shown that M2 macrophages were divided into four sub-phenotypes (M2a, M2b, M2c and M2d) with different functions, and manuscripts have also confirmed that macrophages co-cultured with MSCs were not matched with known four phenotype macrophages. Therefore, our study explored the phenotype and related gene expressions of macrophages in the adipose tissue of T2D mice with/without MSCs infusion.</p></div><div><h3>Methods</h3><p>We induced a T2D mouse model by using high-fat diets and streptozotocin (STZ) injection. The mice were divided into three groups: the control group, the T2D group, and the MSCs group. MSCs were systemically injected once a week for 6 weeks. The phenotype of macrophages in adipose tissue was detected via flow cytometric analysis. We also investigated the gene expression of macrophages in different groups via SMART-RNA-sequencing and quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR).</p></div><div><h3>Results</h3><p>The present study found that the macrophages of adipose tissue in the MSCs group were polarized to the M2 phenotype mixed with four sub-phenotypes. Besides, M2a and M2c held a dominant position, while M2b and M2d (tumor-associated macrophages, TAMs) exhibited a decreasing trend after infusion of MSCs. Moreover, the MSCs group did not appear to express higher levels of tumor-associated, inflammation-associated, or fibrosis-associated genes in comparison to the T2D group.</p></div><div><h3>Conclusion</h3><p>The present results unveiled that the macrophage phenotype was inclined to be present in a hybridity state of four M2 sub-phenotypes and the genes related to tumor-promoting, pro-inflammation and pro-fibrosis were not increased after MSCs injection.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 2","pages":"Article 152788"},"PeriodicalIF":2.8,"publicationDate":"2024-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000068/pdfft?md5=e8e42f730f82ec16086a6241e9f37293&pid=1-s2.0-S0171298524000068-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139579509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evaluation of the serum levels of CCL2, CCL3, and IL-29 after first and second administrations of the COVID-19 vaccine (Oxford–AstraZeneca)","authors":"Zahra Bagheri-Hosseinabadi , Ayat Kaeidi , Mahdi Rezvani , Gholamhossein Taghipour Khaje Sharifi , Mitra Abbasifard","doi":"10.1016/j.imbio.2024.152789","DOIUrl":"10.1016/j.imbio.2024.152789","url":null,"abstract":"<div><h3>Background</h3><p>Previous studies show that chemokines and cytokines play a very important role in eliciting an appropriate response against viruses. Vaccination causes inflammation in the person receiving the vaccine, accompanied with production of inflammatory molecules by immune cells. The more and better the production and expression of chemokines and cytokines by immune cells, the better the response of the acquired immune system. Chemokines and cytokines are critical in promoting the innate immune response against the COVID-19. Here we intended to assess serum levels of CCL2, CCL3, and interleukin (IL)-29 in patients received COVID-19 vaccine.</p></div><div><h3>Methods</h3><p>In this study, 40 subjects vaccinated with the Oxford–AstraZeneca COVID-19 vaccine were selected. Blood samples were collected before injection of the vaccine, 3–5 days after the first dose injection, and 3–5 days subsequent to the second vaccination. To check the serum level of CCL2, CCL3, and IL-29, ELISA technique was used.</p></div><div><h3>Results</h3><p>Our results indicated that the serum levels of CCL2, CCL3, and IL-29 were significantly higher after first and second dose of vaccination compared to before vaccine administration. Furthermore, serum levels of all these mediators were higher after second dose of vaccine compared to the first vaccine administration.</p></div><div><h3>Conclusions</h3><p>Oxford–AstraZeneca COVID-19 vaccine is able to induce inflammatory CCL2 and CCL3 chemokines as well as protective interferon lambda (IL-29).</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 2","pages":"Article 152789"},"PeriodicalIF":2.8,"publicationDate":"2024-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S017129852400007X/pdfft?md5=48cdf5d1950de614021469356fe3ada8&pid=1-s2.0-S017129852400007X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139590357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hyperglycemia modulates M1/M2 macrophage polarization in chronic diabetic patients with pulmonary tuberculosis infection","authors":"Sudhasini Panda , Alisha Arora , Kalpana Luthra , Anant Mohan , Naval K Vikram , Neeraj Kumar Gupta , Archana Singh","doi":"10.1016/j.imbio.2024.152787","DOIUrl":"10.1016/j.imbio.2024.152787","url":null,"abstract":"<div><p>Increased susceptibility to bacterial infections like tuberculosis (TB) is one of the complications of type 2 diabetes, however the underlying mechanisms remains poorly characterized. To explore how chronic hyperglycemia in diabetes affects progression of active TB, we examined mRNA expression of M1 (proinflammatory) and M2 (anti-inflammatory) cytokines/markers, in monocyte-derived macrophages obtained from patients with PTB + DM (pulmonary TB + diabetes mellitus type 2), patients with DM alone, patients with PTB alone, and healthy individuals (controls). Our findings indicate a dysregulated cytokine response in patients with both PTB and DM, characterized by decreased expression levels of interferon-gamma (IFN-γ) and inducible nitric oxide synthase (iNOS), along with increased expression levels of interleukin-1 beta (IL-1β) and CD206. Furthermore, we observed a positive correlation of IL-1β and CD206 expression with levels of glycosylated hemoglobin (HbA1c) in both PTB + DM and DM groups, while IFN-γ showed a positive correlation with HbA1c levels, specifically in the PTB + DM group. Additionally, M1 cytokines/markers, IL-1β and iNOS were found to be significantly associated with the extent of sputum positivity in both PTB and PTB + DM groups, suggesting it to be a function of increased bacterial load and hence severity of infection. Our data demonstrates that tuberculosis in individuals with PTB + DM is characterized by altered M1/M2 cytokine responses, indicating that chronic inflammation associated with type 2 diabetes may contribute to increased immune pathology and inadequate control of tuberculosis infection.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 2","pages":"Article 152787"},"PeriodicalIF":2.8,"publicationDate":"2024-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000056/pdfft?md5=71e1a0429a554537b9343ade21ed6d95&pid=1-s2.0-S0171298524000056-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139458950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ImmunobiologyPub Date : 2024-01-10DOI: 10.1016/j.imbio.2024.152783
Yajun Zhao , Jiangtao Wang , Xiaodong Liang , Chen Wang
{"title":"Clinical relevance of ORCs in predicting prognosis and immunotherapy outcomes: A pan-cancer analysis","authors":"Yajun Zhao , Jiangtao Wang , Xiaodong Liang , Chen Wang","doi":"10.1016/j.imbio.2024.152783","DOIUrl":"https://doi.org/10.1016/j.imbio.2024.152783","url":null,"abstract":"<div><h3>Background</h3><p>The origin recognition complex (ORC) consists of six subunits and mediates DNA replication by binding to its origin. Recent studies show that ORCs are closely related to various biological processes in tumors. However, a comprehensive study of ORCs in pan-cancer has not been conducted.</p></div><div><h3>Results</h3><p>A systematic evaluation of the expression, mutation, and prognostic significance of ORCs was conducted across cancer types using data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. The single-sample Gene Set Enrichment Analysis (ssGSEA) was performed using R package “Gene Set Variation Analysis (GSVA)” to evaluate ORC score. ORC score was significantly elevated in most cancers and linked with an inferior prognosis. It was positively related to the G2/M checkpoint and DNA repair pathways. An elevated ORC score also correlated with tumor mutation burden (TMB)/ microsatellite instability (MSI). A prognosis analysis suggested that high ORC scores were associated with heightened immunotherapeutic sensitivity.</p></div><div><h3>Conclusions</h3><p>Our research elucidates the genomic changes associated with and clinical relevance of ORCs in cancer and provides unique insights for future investigation of ORCs in immunotherapy.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 2","pages":"Article 152783"},"PeriodicalIF":2.8,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000019/pdfft?md5=1bca731bc80cb958912565d9382ca5e8&pid=1-s2.0-S0171298524000019-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139419213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ImmunobiologyPub Date : 2024-01-01DOI: 10.1016/j.imbio.2023.152780
Su In Lee , Haneul Kim , Chang Ki Lim , Jae Dong Kim , Jeong Seok Heo , Joongoo Jung , Chan Kim , Hong Jae Chon , Jae-Won Jeon
{"title":"Engagement of CD300c by a novel monoclonal antibody induces the differentiation of monocytes to M1 macrophages","authors":"Su In Lee , Haneul Kim , Chang Ki Lim , Jae Dong Kim , Jeong Seok Heo , Joongoo Jung , Chan Kim , Hong Jae Chon , Jae-Won Jeon","doi":"10.1016/j.imbio.2023.152780","DOIUrl":"10.1016/j.imbio.2023.152780","url":null,"abstract":"<div><p>Human CD300c is expressed on various immune or cancer cells and is a novel B7 family member, functioning as an activity modulator on immune cells. To elucidate the function of CD300c, we developed CL7, a human CD300c-specific monoclonal antibody, and assessed its biological activity. The specific binding of CL7 monoclonal antibody against recombinant CD300c antigen was confirmed using enzyme-linked immunosorbent assay and surface plasmon resonance analysis. The binding affinity of CL7 was strong at the sub-nanomolar level. Furthermore, CL7 effectively bound to exogenously expressed CD300c on 293T cells. CL7 antibody differentiated monocytes to M1 macrophages, as evidenced by the upregulated expression of M1-specific cell surface markers and increased secretion of M1-specific cytokines in vitro in THP-1 cells and primary macrophages, as well as the increased population size of M1 macrophages in tumors grafted into mice. Additionally, CL7 treatment upregulated PD-L1 expression on THP-1 cells. We confirmed that the mechanism of M1 macrophage differentiation was through the mitogen-activated protein kinase and NF-κB signaling pathways. CD300c expression on various immune and cancer cells was similar to that of the well-known immune checkpoint PD-L1, suggesting the possibility of CD300c as a novel tumor biomarker. We also confirmed that the tumor size was substantially reduced by CL7 antibody treatment in the CT26 mouse model. Our study supports that CD300c is a potential therapeutic target in immuno-oncology. Overall, the CD300c-specific monoclonal antibody, CL7, is a promising immunotherapeutic agent, and it induces enhanced differentiation of M1 macrophages and/or their infiltration into the tumor microenvironment.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 1","pages":"Article 152780"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298523045825/pdfft?md5=375758e9582e44f7c9f0f15ee884fde0&pid=1-s2.0-S0171298523045825-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139024830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ImmunobiologyPub Date : 2024-01-01DOI: 10.1016/j.imbio.2023.152778
Chengyue Zhou , Dan Han , Hui Fang , Dake Huang , Heping Cai , Yujun Shen , Yuxian Shen , Jun Liu
{"title":"Deletion of mesencephalic astrocyte-derived neurotrophic factor delays and damages the development of white pulp in spleen","authors":"Chengyue Zhou , Dan Han , Hui Fang , Dake Huang , Heping Cai , Yujun Shen , Yuxian Shen , Jun Liu","doi":"10.1016/j.imbio.2023.152778","DOIUrl":"10.1016/j.imbio.2023.152778","url":null,"abstract":"<div><p>Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER) stress-induced protein, and it has been reported that ER stress and unfolded protein response (UPR) are closely related to the immune system. The spleen is an important immune organ and we have shown in our previous research that MANF is expressed in human spleen tissues. However, there have been limited studies about the effect of MANF on spleen development. In this study, we detected MANF expression in spleen tissues and found that MANF was expressed in the red pulp and marginal zone. Additionally, MANF was localized in the CD68<sup>+</sup> and CD138<sup>+</sup> cells of adult rat spleen tissues, but not in the CD3<sup>+</sup> cells. We performed immunohistochemical staining to detect MANF expression in the spleen tissues of rats that were different ages, and we found that MANF<sup>+</sup> cells were localized together in the spleen tissues of rats that were 1–4 weeks old. MANF was also expressed in CD68<sup>+</sup> cells in the spleen tissues of rats and mice. Furthermore, we found that MANF deficiency inhibited white pulp development in MANF knockout mice, thus indicating that MANF played an important role in the white pulp development of rodent spleen tissues.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 1","pages":"Article 152778"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298523045801/pdfft?md5=e0df5365e5a9b2d2236b47d425aae6ab&pid=1-s2.0-S0171298523045801-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138987151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ImmunobiologyPub Date : 2024-01-01DOI: 10.1016/j.imbio.2023.152781
Chenxi Ma , Jiasheng Wu , Hongwei Lei , He Huang , Yingnan Li
{"title":"Significance of m6A in subtype identification, immunological evolution, and therapeutic sensitivity of RA","authors":"Chenxi Ma , Jiasheng Wu , Hongwei Lei , He Huang , Yingnan Li","doi":"10.1016/j.imbio.2023.152781","DOIUrl":"10.1016/j.imbio.2023.152781","url":null,"abstract":"<div><p>N6-methyladenosine (m6A) is one kind of important epigenetic modification pattern which is extensively involved in immune regulation. The development and progression of autoimmune diseases are closely related to immune dysregulation. Considering that rheumatoid arthritis (RA) is a typical autoimmune disease, the m6A process might be one of the important regulatory mechanisms in the pathogenesis of RA. In this study, we identified five differentially expressed m6A regulators in normal and RA samples from the GEO database. With these five regulators, we constructed the nomogram, and it could accurately identify the risk of RA morbidity. Next, we identified 121 differentially expressed genes (DEGs) between normal and RA samples, of which 36 DEGs were co-expressed with these five m6A regulators. We noted that these DEGs were highly enriched in multiple immunoregulatory signaling pathways, such as cytokine-mediated immune cell chemotaxis, adhesion, and activation. To further characterize the heterogeneity of immunological features, we clustered the RA samples into two subtypes. The C2 subtype has higher infiltration levels of pro-inflammatory cells and activity of pro-inflammatory signaling pathways. Thus, the inflammatory response might be more vigorous in the C2 subtype. Next, we constructed the m6Asig system with the SVM machine learning algorithms and least absolute shrinkage and selection operator (LASSO) regression. The m6Asig could accurately distinguish the C1 and C2 subtypes, which indicated that the m6Asig could be a potential biomarker for the inflammatory activity of RA. Finally, by comparing the information from the CellMiner, TTD, and DrugBank databases, we determined 25 drugs. The targets of these drugs were positively correlated with m6Asig. To be clarified, the above findings were derived from bioinformatics and statistical analyses, and further experimental validation still requires. In summary, this study further revealed the m6A and immunoregulation mechanisms in RA pathogenesis. Also, the m6Asig could be a novel biomarker with potential applicability in the clinical management of RA.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 1","pages":"Article 152781"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298523045837/pdfft?md5=d760a30c22492641861650222d6e0b83&pid=1-s2.0-S0171298523045837-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139015122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}