Immunobiology最新文献

{"title":"Identification of RNMT as an immunotherapeutic and prognostic biomarker: From pan-cancer analysis to lung squamous cell carcinoma validation","authors":"Shuqiang Huang ,&nbsp;Cuiyu Tan ,&nbsp;Jinzhen Zheng ,&nbsp;Zhugu Huang ,&nbsp;Zhihong Li ,&nbsp;Ziyin Lv ,&nbsp;Wanru Chen ,&nbsp;Miaoqi Chen ,&nbsp;Xiaojun Yuan ,&nbsp;Cairong Chen ,&nbsp;Qiuxia Yan","doi":"10.1016/j.imbio.2024.152836","DOIUrl":"10.1016/j.imbio.2024.152836","url":null,"abstract":"<div><h3>Background</h3><p>Dysregulation of RNA guanine-7 methyltransferase (RNMT) plays a crucial role in the tumor progression and immune responses. However, the detailed role of RNMT in pan-cancer is still unknown.</p></div><div><h3>Methods</h3><p>Bulk transcriptomic data of pan-cancer were obtained from the Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Cancer Cell Line Encyclopedia (CCLE) databases. Single-cell transcriptomic and proteomics data of lung squamous cell carcinoma (LUSC) were analyzed in the Tumor Immune Single-cell Hub 2 (TISCH2) and Clinical Proteomic Tumor Analysis Consortium (CPTAC) databases, respectively. The correlation between RNMT expression and cancer prognosis was analyzed by Cox proportional hazards regression and Kaplan–Meier analyses. The correlation of RNMT expression with common immunoregulators, tumor mutation burden (TMB), microsatellite instability (MSI), mismatch repair (MMR), and DNA methyltransferase (DNMT) was analyzed. Additionally, the correlation between RNMT expression and immune infiltration level was evaluated. A total of 1287 machine learning combinations were used to construct prognostic models for LUSC. qRT-PCR and Western blot were used to validate the bioinformatics findings of RNMT upregulation in LUSC.</p></div><div><h3>Results</h3><p>RNMT was widely expressed across different cancers, with significant correlation to prognosis in cancers such as kidney chromophobe (KICH) (<em>p</em> = 0.0033, HR = 7.12), liver hepatocellular carcinoma (LIHC) (<em>p</em> = 0.01, HR = 1.41), and others. Notably, RNMT participates in the regulation of the tumor microenvironment. RNMT expression positively correlated with immune cell expression (Spearman’s rank correlation, <em>p</em> &lt; 0.05). Moreover, RNMT expression was strongly associated with immunoregulators, TMB, MSI, MMR, and DNMT in most cancer types. Notably, RNMT expression displayed excellent prognostic and immunological performance in LUSC. The expression of RNMT was mainly enriched in B cells of LUSC tissues. qRT–PCR and Western blot verified the high expression of RNMT in LUSC.</p></div><div><h3>Conclusion</h3><p>RNMT expression widely correlated with prognosis and immune infiltration in various tumors, especially LUSC. The RNMT detection may provide a new idea for future tumor immune studies and treatment strategies.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 5","pages":"Article 152836"},"PeriodicalIF":2.5,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000548/pdfft?md5=73725e141da91879048855347e08171d&pid=1-s2.0-S0171298524000548-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141630455","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":"HNRNP I promotes IRAK1 degradation to reduce podocyte apoptosis and inflammatory response alleviating renal injury in diabetic nephropathy","authors":"Zichen Rao ,&nbsp;Geriletu Ao ,&nbsp;Yiming Zhang ,&nbsp;Zhifen Jiang ,&nbsp;Liping Li ,&nbsp;Zhidan Hua","doi":"10.1016/j.imbio.2024.152835","DOIUrl":"10.1016/j.imbio.2024.152835","url":null,"abstract":"<div><p>Podocytes maintain renal filtration integrity when the glomerular filtration barrier (GFB) is integrated. Impairment or attrition of podocytes, leading to compromised GFB permeability, constitutes the primary etiology of proteinuria and is a hallmark pathological feature of diabetic nephropathy (DN). This study centers on Heterogeneous Nuclear Ribonucleoprotein I (HNRNP I), an RNA-binding protein, delineating its role in facilitating DN-induced renal damage by modulating podocyte health. Comparative analyses in renal biopsy specimens from DN patients and high-glucose-challenged podocyte models in vitro revealed a marked downregulation of HNRNP I expression relative to normal renal tissues and podocytes. In vitro assays demonstrated that high-glucose conditions precipitated a significant reduction in podocyte viability and an escalation in markers indicative of apoptosis. Conversely, HNRNP I overexpression was found to restore podocyte viability and attenuate apoptotic indices. IRAK1, a gene encoding a protein integral to inflammatory signaling, was shown to interact with HNRNP I, which promotes IRAK1 degradation. This interaction culminates in suppressing the PI3K/AKT/mTOR signaling pathway, thereby diminishing podocyte apoptosis and mitigating renal damage in DN. This investigation unveils the mechanistic role of HNRNP I in DN for the first time, potentially informing novel therapeutic strategies for DN renal impairment.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 5","pages":"Article 152835"},"PeriodicalIF":2.5,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000536/pdfft?md5=19e3f2974a6bb8d6a3a34fae220aa324&pid=1-s2.0-S0171298524000536-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579530","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":"Chimeric antigen carried by extracellular vesicles induces stronger protective immunity against Mycobacterium tuberculosis infection","authors":"Lin Ji ,&nbsp;Yuxuan Fu ,&nbsp;Sidong Xiong","doi":"10.1016/j.imbio.2024.152834","DOIUrl":"10.1016/j.imbio.2024.152834","url":null,"abstract":"<div><p>Although Bacillus Calmette-Guerin (BCG) has been used in human for centuries, tuberculosis (TB) remains one of the deadliest infectious diseases.<!--> <!-->There have been remarkable successes in the field of TB vaccine research over the past decade, but the search for a better vaccine candidate is still a challenge. Extracellular vesicles (EVs) possess a multitude of properties that make them attractive candidates for the development of novel, cell-free, non-replicative, and safe vaccine system. These properties include their small size, inherent immunogenicity, ability to be taken up by immune cells, self-adjuvant capability and the comprehensive distribution of concentrated antigens. In this study, we designed a newly chimeric antigen TB vaccine (CA) with three <em>Mycobacterium tuberculosis</em> (<em>M. tb</em>) antigens that identified from extracellular vesicle derived from <em>M. tb</em>-infected macrophage. We confirmed that the CA stimulated a more pronounced immune response and enhanced T-cell activation, thereby providing superior protection against <em>Mycobacterium tuberculosis</em> infection in comparison to the bivalent antigens. Importantly, the EVs carrying CA (EVs-CA) provided enhanced protection against <em>M. tb</em> infection compared to unencapsulated CA antigen. Moreover, we established an EV-carried CA system (EVs-CA) and released from a transformed cell line using endogenous loading of antigen method. This method displayed the CA could efficiently package into EVs and increased concentration of this antigen. The chimeric antigen carried by EVs induced higher levels of cytokines production and specific cytotoxic T lymphocytes, resulted in enhancing antibody response and improving protective efficacy. Our findings suggested that the potential of EVs as delivery system to carry the <em>M. tb</em>-specific chimeric antigen for controlling <em>Mycobacterium tuberculosis</em> infection.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 5","pages":"Article 152834"},"PeriodicalIF":2.5,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000524/pdfft?md5=db6c0a642fb0a90d846e030f4f875186&pid=1-s2.0-S0171298524000524-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141537874","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":"Chronic NOD2 stimulation by MDP confers protection against parthanatos through M2b macrophage polarization in RAW264.7 cells","authors":"Florencia C. Mansilla ,&nbsp;María C. Miraglia ,&nbsp;Silvina S. Maidana ,&nbsp;Randazzo Cecilia ,&nbsp;Alejandra V. Capozzo","doi":"10.1016/j.imbio.2024.152833","DOIUrl":"10.1016/j.imbio.2024.152833","url":null,"abstract":"<div><p>Innate immune cells show enhanced responsiveness to secondary challenges after an initial non-related stimulation (Trained Innate Immunity, TII). Acute NOD2 activation by Muramyl-Dipeptide (MDP) promotes TII inducing the secretion of pro-inflammatory mediators, while a sustained MDP-stimulation down-regulates the inflammatory response, restoring tolerance. Here we characterized <em>in-vitro</em> the response of murine macrophages to lipopolysaccharide (LPS) challenge under NOD2-chronic stimulation. RAW264.7 cells were trained with MDP (1 μg/ml, 48 h) and challenged with LPS (5 μg/ml, 24 h). Trained cells formed multinucleated giant cells with increased phagocytosis rates compared to untrained/challenged cells. They showed a reduced mitochondrial activity and a switch to aerobic glycolysis. TNF-α, ROS and NO were upregulated in both trained and untrained cultures (MDP+, MDP- cells, p &gt; 0.05); while IL-10, IL-6 IL-12 and MHCII were upregulated only in trained cells after LPS challenge (MDP + LPS+, p &lt; 0.05). A slight upregulation in the expression of B7.2 was also observed in this group, although differences were not statistically significant. MDP-training induced resistance to LPS challenge (p &lt; 0.01). The relative expression of PARP-1 was downregulated after the LPS challenge, which may contribute to the regulatory milieu and to the innate memory mechanisms exhibited by MDP-trained cells. Our results demonstrate that a sustained MDP-training polarizes murine macrophages towards a M2b profile, inhibiting parthanatos. These results may impact on the development of strategies to immunomodulate processes in which inflammation should be controlled.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 5","pages":"Article 152833"},"PeriodicalIF":2.5,"publicationDate":"2024-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000512/pdfft?md5=5b26f53f6b3e94bc6fe5b9a0bc161bd3&pid=1-s2.0-S0171298524000512-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141534288","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":"Mitochondrial activity related genes of mast cells identify poor prognosis and metastasis of ovarian cancer","authors":"Xinghua Ma ,&nbsp;Caryl Ligan ,&nbsp;Shijia Huang ,&nbsp;Yirong Chen ,&nbsp;Muxin Li ,&nbsp;Yuanyuan Cao ,&nbsp;Wei Zhao ,&nbsp;Shuli Zhao","doi":"10.1016/j.imbio.2024.152831","DOIUrl":"10.1016/j.imbio.2024.152831","url":null,"abstract":"<div><p>The pro-tumorigenic or anti-tumorigenic role of tumor infiltrating mast cells (TIMs) in tumors depends not only on the type of cancer and the degree of tumor progression, but also on their location in the tumor bulk. In our investigation, we employed immunohistochemistry to reveal that the mast cells (MCs) in the tumor stroma are positively correlated with metastasis of ovarian cancer (OC), but not in the tumor parenchyma. To delve deeper into the influence of different culture matrix stiffness on MCs’ biological functions within the tumor parenchymal and stromal regions, we conducted a transcriptome analysis of the mouse MC line (P815) cultured in two-dimensional (2D) or three-dimensional (3D) culture system. Further research has found that the softer 3D extracellular matrix stiffness could improve the mitochondrial activity of MCs to promote proliferation by increasing the expression levels of mitochondrial activity-related genes, namely Pet100, atp5md, and Cox7a2. Furthermore, employing LASSO regression analysis, we identified that Pet100 and Cox7a2 were closely associated with the prognosis of OC patients. These two genes were subsequently employed to construct a risk score model, which revealed that the high-risk group model as one of the prognostic factors for OC patients. Additionally, the XCell algorithm analysis showed that the high-risk group displayed a broader spectrum of immune cell infiltrations. Our research revealed that TIMs in the tumor stroma could promote the metastasis of OC, and mitochondrial activity-related proteins Pet100/Cox7a2 can serve as biomarkers for prognostic evaluation of OC.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 5","pages":"Article 152831"},"PeriodicalIF":2.5,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000494/pdfft?md5=9719b11813432b1e4d076545a00c32df&pid=1-s2.0-S0171298524000494-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467622","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":"WIP1-mediated regulation of p38 MAPK signaling attenuates pyroptosis in sepsis-associated acute kidney injury","authors":"Yinhong Wang ,&nbsp;Chenkai Cui ,&nbsp;Weihao Zhao ,&nbsp;Xuefei Tian ,&nbsp;Pengfei Liu ,&nbsp;Linting Wei ,&nbsp;Zikun Zhu ,&nbsp;Ming Liu ,&nbsp;Rongguo Fu ,&nbsp;Lining Jia","doi":"10.1016/j.imbio.2024.152832","DOIUrl":"10.1016/j.imbio.2024.152832","url":null,"abstract":"<div><p>Wild-Type p53-Induced Phosphatase 1 (WIP1/PPM1D) is a serine/threonine phosphatase that plays a significant role in various physiological processes. However, the involvement of WIP1 in kidney remains unclear. Lipopolysaccharide (LPS) was administered to induce acute injury in mice and human kidney 2 (HK2) cells in the study. The WIP1 inhibitor, CCT007093, was administered both in vitro and in vivo to assess its effect on kidney. The single-cell sequencing (scRNA-seq) data revealed that <em>Ppm1d</em> mRNA reached peak on day 2 following unilateral ischemia–reperfusion injury (uni-IRI) in mice, especially in the proximal renal tubules during repair phase. Compared to the control group, WIP1 protein exhibited a significant increase in renal tubules of patients with acute tubular injury (ATI) and mice with LPS-induced acute kidney injury (AKI), as well as in LPS-injured HK2 cells. In vitro experiments showed that CCT007093 increased the protein levels of NLRP3, cleaved-Caspase1, GSDMD-N and IL-1β in HK2 cells and further reduced the viability of LPS-stimulated HK2 cells. In vivo experiments showed that inhibition of WIP1 activity with CCT007093 further increased cleaved-Caspase1, GSDMD-N protein levels in kidney tissue from mice with LPS-induced AKI. In addition, LPS induces phosphorylation of p38 MAPK, a key regulator of pyroptosis, which is further activated by CCT007093. In conclusion, inhibition of WIP1 activity acts as a positive regulator of renal tubular pyroptosis mainly through the mediation of phospho-p38 MAPK.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 5","pages":"Article 152832"},"PeriodicalIF":2.5,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000500/pdfft?md5=ef71be66f2da69ef33aedbc6a1030a22&pid=1-s2.0-S0171298524000500-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467623","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":"CD8 T lymphocytes from B-1 cell-deficient mice down-regulates fungicidal activity of macrophages challenged with E. Cuniculi","authors":"Cristina Gabriela Nascimento de Oliveira,&nbsp;Elizabeth Cristina Perez,&nbsp;Anuska Marcelino Alvares-Saraiva,&nbsp;Maria Anete Lallo","doi":"10.1016/j.imbio.2024.152827","DOIUrl":"https://doi.org/10.1016/j.imbio.2024.152827","url":null,"abstract":"<div><h3>Background</h3><p><em>Encephalitozoon cuniculi</em> is an opportunistic intracellular pathogen that establishes a balanced relationship with immunocompetent individuals depending on the activity of their CD8⁺ T cells lymphocytes. However, lower resistance to experimental infection with <em>E. cuniculi</em> was found in B-1 deficient mice (Xid), besides increased the number of CD8 T lymphocytes. Here, we evaluated the profile of CD8⁺ T lymphocytes from Balb/c wild-type (WT) or Balb/c Xid mice (with B-1 cell deficiency) on the microbicidal activity of macrophages challenged with <em>E. cuniculi</em>.</p></div><div><h3>Methods</h3><p>Naïve CD8 T lymphocytes from WT or Xid mice uninfected and primed CD8 T lymphocytes from WT or Xid mice infected with <em>E cuniculi</em> were co-cultured with macrophages previously challenged with <em>E. cuniculi</em>. We evaluated macrophages viability and microbicidal activity, and CD8 T lymphocytes viability and presence of activating molecules (CD62L, CD69, and CD107a).</p></div><div><h3>Results</h3><p>Macrophages co-cultured with naïve CD8 T lymphocytes from WT demonstrated high microbicidal activity. Naïve CD8 T lymphocytes obtained from WT mice had a higher expression of CD69 and LAMP-1-activating molecules compared to Xid CD8⁺ T lymphocytes. Primed CD8 T lymphocytes from Xid mice proliferated more than those from WT mice, however, when the expression of the activating molecule CD69 associated with the expression of CD62L was kept low. In conclusion, naïve CD8⁺ T lymphocytes from Xid mice, deficient in B-1 cells, they had reduced expression of activation molecules and cytotoxic activity.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 4","pages":"Article 152827"},"PeriodicalIF":2.8,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000457/pdfft?md5=b1fa9ca2514ee417bd706d59ba2826d6&pid=1-s2.0-S0171298524000457-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141323051","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":"Exploring the role of pyroptosis and immune infiltration in sepsis based on bioinformatic analysis","authors":"Zhi-hua Li,&nbsp;Yi Wang,&nbsp;Xiang-you Yu","doi":"10.1016/j.imbio.2024.152826","DOIUrl":"10.1016/j.imbio.2024.152826","url":null,"abstract":"<div><h3>Purpose</h3><p>Sepsis is a disease that is typically treated in intensive care units with high mortality and morbidity. Pyroptosis is a newly identified type of programmed cell death and is characterized by inflammatory cytokine secretion. However, the role of pyroptosis in sepsis remains unclear.</p></div><div><h3>Methods</h3><p>GSE28750 and GSE134347 datasets were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed pyroptosis genes (DEPGs) were identified between sepsis and healthy controls. Machine learning was used to further narrow the gene range. Receiver operating curves (ROC) were generated to estimate the diagnostic efficacy. Immune infiltration levels were estimated via single-sample gene set enrichment analysis (ssGSEA). A network database was used to predict the upstream transcription factors and miRNAs of DEPGs. Finally, the expression of the genes was validated by qRT-PCR between sepsis patients and healthy controls.</p></div><div><h3>Results</h3><p>We found that the pyroptosis pathway was enriched and activated in sepsis. 8 DEPGs were identified. A heatmap showed that the genes, NLRC4, NAIP, IL-18, AIM2 and ELANE, were abundant in the sepsis samples, and the genes, NLRP1, CHMP7 and TP53, were abundant in the healthy control samples. The ssGSEA results showed that the abundances of activated dendritic cells, MDSC, macrophage, plasmacytoid dendritic cells, regulatory T-cells, and Th17-cells were significantly higher, while the activated B-cell, activated CD8 T-cell, CD56 dim tural killer cell, immature B-cell, monocyte, and T follicular helper cell abundances were lower in sepsis samples compared to healthy controls. The qRT-PCR results showed that the expression levels of NAIP, IL-18, TP53, CHMP7, NLRC4, ELANE and NLRP1 were consistant with the bioinformatic analyses, while the expression level of AIM2 has no significant difference.</p></div><div><h3>Conclusion</h3><p>Our study identified seven potential pyroptosis-related genes, NAIP, IL-18, TP53, CHMP7, NLRC4, ELANE and NLRP1. This study revealed that pyroptosis may promote sepsis development by activating the immune response.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 5","pages":"Article 152826"},"PeriodicalIF":2.5,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000445/pdfft?md5=6e8101f3053c6d00afaa0af283ad3480&pid=1-s2.0-S0171298524000445-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141405282","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":"Increased inhibitory surface marker PD-1 expression in CD4+T cells and Th2+T cells in allergen-specific immunotherapy","authors":"Xueyan Jie,&nbsp;Dan Wang,&nbsp;Hongju Da,&nbsp;Hongxin Li,&nbsp;Hongyan Zhao,&nbsp;Jin He,&nbsp;Jianghao Liu,&nbsp;Yu Ma,&nbsp;Zhihui Qiang,&nbsp;Zhuoyang Li,&nbsp;Haicheng Zhong,&nbsp;Yun Liu","doi":"10.1016/j.imbio.2024.152824","DOIUrl":"10.1016/j.imbio.2024.152824","url":null,"abstract":"<div><p>Recent evidence has shown that T cell exhaustion is implicated in Allergen-specific Immunotherapy (AIT). However, how T cell exhaustion plays a role in AIT is far from clear. Our study aimed to investigate T cell exhaustion associated with allergen exposure during AIT in mice. Ovalbumin (OVA) − sensitized C57BL/6J asthma mouse and AIT mouse models were constructed. Quantitative real-time PCR (qRTPCR) and flow cytometry were used to monitor the occurrence of local and systemic CD4⁺ T cells and Th2⁺T cells exhaustion in OVA-sensitized mice. The inhibitory surface marker programmed cell death protein 1 (PD-1) on CD4⁺ T cells and Th2⁺T cells was significantly upregulated in AIT mice compared with asthmatic and control mice. The level of PD-1 on the surface of CD4⁺T cells of asthma mice was significantly higher than that of control mice. The inhibitory surface marker cytotoxic T lymphocyte-associated protein 4 (CTLA-4) on CD4⁺ T cells and Th2⁺T cells showed no significant difference between the AIT, asthma and control mice. Collectively, our study indicated that the expression of PD-1 on CD4⁺ T cells and Th2⁺T cells was increased in AIT. Allergen exposure promotes the expression of PD-1 on the surface of CD4⁺ T cells. T cell exhaustion plays an important role in AIT.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 4","pages":"Article 152824"},"PeriodicalIF":2.8,"publicationDate":"2024-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000421/pdfft?md5=f8679ed2bde9c5795007f010aaed4c13&pid=1-s2.0-S0171298524000421-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141320762","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":"Exploring liquid-liquid phase separation-related diagnostic biomarkers in osteoarthritis based on machine learning algorithms and experiment","authors":"","doi":"10.1016/j.imbio.2024.152825","DOIUrl":"10.1016/j.imbio.2024.152825","url":null,"abstract":"<div><h3>Background</h3><p>Osteoarthritis (OA) is a prevalent joint disorder characterized by cartilage degeneration and joint inflammation. Liquid-liquid phase separation (LLPS), a biophysical process involved in cellular organization, has recently gained attention in OA research. However, the relationship between LLPS and OA remains poorly understood.</p></div><div><h3>Methods</h3><p>We analyzed gene expression data from the GSE48556 dataset to identify LLPS-related genes associated with OA. Differential expression analysis, enrichment analyses, and machine learning algorithms were employed to explore the functional significance of LLPS-related genes in OA and then construct a diagnostic model for OA. In addition, IL-1β as a pro-inflammatory factor to establish an <em>in vitro</em> OA model, and the protein expression levels of OA biomarkers were detected by western blot.</p></div><div><h3>Results</h3><p>A total of 145 LLPS-related genes were screened in OA samples. Enrichment analyses revealed these genes were mainly enriched in mRNA metabolic processes, cytoplasmic granules, and insulin resistance. Four characteristic genes for OA were selected by using machine learning algorithms, including ADRB2, H3F3B, GNL3L, and PELO. These genes showed satisfactory diagnostic values. Furthermore, there were association between these biomarkers and immune cells, including T cells CD8 and monocytes. <em>In vitro</em> experiments showed that IL-1β stimulation significantly inhibited the cell viability of chondrocytes and enhanced the levels of pro-inflammatory factors, that could mimic the inflammatory state of OA. The expression levels of GNL3L and H3F3B proteins in IL-1β group were obviously lower than those in control group, while levels of ADRB2 and PELO were higher, which was consistent with the results of bioinformatics analysis.</p></div><div><h3>Conclusion</h3><p>Our study identifies LLPS-related genes as potential diagnostic biomarkers for OA. These findings provide insights into the molecular mechanisms underlying OA pathogenesis and offer opportunities for the development of novel therapeutic strategies.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 5","pages":"Article 152825"},"PeriodicalIF":2.5,"publicationDate":"2024-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000433/pdfft?md5=eb2e72ca2e466c1becb11114915ca223&pid=1-s2.0-S0171298524000433-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141413943","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}