Immunobiology最新文献

{"title":"The role of CD24hiCD27+ regulatory B cells in human chronic rhinosinusitis with/without nasal polyps","authors":"Shiyu Tian ,&nbsp;Jiao Xia ,&nbsp;Ke Liu ,&nbsp;Youxiang Ma ,&nbsp;Hao Tian ,&nbsp;Weiwei Wang ,&nbsp;Ruxiang Zhang ,&nbsp;Chunli Zhao ,&nbsp;Shusheng Gong","doi":"10.1016/j.imbio.2024.152854","DOIUrl":"10.1016/j.imbio.2024.152854","url":null,"abstract":"<div><h3>Background</h3><div>Regulatory B cells (Bregs) reduce allergic and autoimmune inflammation. However, their role in chronic rhinosinusitis (CRS) remains unknown. This study investigated the frequency and function of Breg subsets in the peripheral blood of patients with CRS.</div></div><div><h3>Methods</h3><div>The demographic and clinical characteristics were compared among control, CRSsNP, neCRSwNP, and eCRSwNP groups. The expression of various Breg subtypes was evaluated in peripheral blood mononuclear cells (PBMCs) of patients with eosinophilic CRS with nasal polyps (eCRSwNP), non-eosinophilic CRS with nasal polyps (neCRSwNP), CRS without nasal polyps (CRSsNP). CD19⁺CD24^hiCD27⁺ B cells (B10 cells) were isolated by flow cytometry, followed by RNA sequencing (RNA-seq). Finally, IL-10 secreted by B10 cells were evaluated through the intracellular stain.</div></div><div><h3>Results</h3><div>A higher number of eosinophils in peripheral blood and nasal polyps were found in eCRSwNP compared with neCRSwNP, CRSsNP, and control groups. The frequency of B10 in the peripheral blood B cells (B10%) of patients with eCRSwNP was significantly lower than that in the neCRSwNP and control groups. B10% was negatively correlated with the quantity of tissue eosinophils, and the percentage and absolute value of peripheral blood eosinophils. The eCRSwNP, neCRSwNP and control groups had 1403 differentially expressed genes, 35 of which were identified in four highly enriched pathways. Additionally, the frequency of IL-10⁺B10 cells in peripheral blood was lower in patients with eCRSwNP than in the neCRSwNP and control groups.</div></div><div><h3>Conclusion</h3><div>This study is the first to reveal differences in both the quantity and IL-10 secretion of B10 cells in patients with eCRSwNP and neCRSwNP. These variations were strongly negatively associated with eosinophils in nasal polyps and peripheral blood. IL-10⁺B10 cells may play a key role in the pathological mechanisms of CRS, particularly the recurrence of eCRSwNP.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 6","pages":"Article 152854"},"PeriodicalIF":2.5,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142328254","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":"Retraction notice to “Increased levels of Th17 cells are associated with non-neuronal acetylcholine in COPD patients” [Immunobiology 219(5) (2014) 392–401]","authors":"","doi":"10.1016/j.imbio.2024.152806","DOIUrl":"10.1016/j.imbio.2024.152806","url":null,"abstract":"","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 5","pages":"Article 152806"},"PeriodicalIF":2.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S017129852400024X/pdfft?md5=32799ad5a8cec97d6f1991e1e20c7c50&pid=1-s2.0-S017129852400024X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467621","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":"A study on the efficacy and Safety Evaluation of a novel PD-1/CTLA-4 bispecific antibody","authors":"Qi Song ,&nbsp;Meiling Jiang ,&nbsp;Xinrong Pan ,&nbsp;Guanyue Zhou ,&nbsp;Xiaomeng Zhang","doi":"10.1016/j.imbio.2024.152844","DOIUrl":"10.1016/j.imbio.2024.152844","url":null,"abstract":"<div><p>Tumors constitute a significant health concern for humans, and PD-1 and CTLA-4 monoclonal antibodies have been proven effective in cancer treatment. Some researchers have identified that the combination of PD-1 and CTLA-4 dual blockade demonstrates superior therapeutic efficacy. However, the development of PD-1/CTLA-4 bispecific antibodies faces challenges in terms of both safety and efficacy. The present study discloses a novel PD-1/CTLA-4 bispecific antibody, designated as SH010. Experimental validation through surface plasmon resonance (SPR) confirmed that SH010 exhibits favorable binding activity with both PD-1 and CTLA-4. Flow cytometry analysis demonstrated stable binding of SH010 antibody to CHOK1 cells overexpressing human or cynomolgus monkey PD-1 protein and to 293F cells overexpressing human or cynomolgus monkey CTLA-4 protein. Moreover, it exhibited excellent blocking capabilities in protein binding between human PD-1 and PD-L1, as well as human CTLA-4 and CD80/CD86. Simultaneously, in <em>vitro</em> experiments indicate that SH010 exerts a significant activating effect on hPBMCs. In murine transplant models of human prostate cancer (22RV1) and small cell lung cancer (NCI-H69), administration of varying concentrations of the bispecific antibody significantly inhibits tumor growth. MSD analysis revealed that stimulation of hPBMCs from three different donors with SH010 did not induce the production of cytokine release syndrome. Furthermore, Single or repeated intravenous administrations of SH010 in cynomolgus monkeys show favorable systemic exposure without noticeable drug accumulation or apparent toxicity. In conclusion, SH010 represents a novel cancer therapeutic drug poised to enter clinical trials and obtain market approval.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 6","pages":"Article 152844"},"PeriodicalIF":2.5,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000627/pdfft?md5=f6449ebbf3632fd4a2aaa2465393d152&pid=1-s2.0-S0171298524000627-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125607","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":"Myeloperoxidase-deficient mice exposed to Zymosan exhibit severe neutrophilia and anemia with enhanced granulopoiesis and reduced erythropoiesis, accompanied by pulmonary inflammation","authors":"Misaki Yoshikawa ,&nbsp;Yuki Sato ,&nbsp;Mayu Sasaki ,&nbsp;Yasuaki Aratani","doi":"10.1016/j.imbio.2024.152843","DOIUrl":"10.1016/j.imbio.2024.152843","url":null,"abstract":"<div><p>We previously reported that myeloperoxidase-deficient (MPO^-/-) mice develop more severe neutrophil-rich lung inflammation than wild-type mice following intranasal Zymosan administration. Interestingly, we found that these mutant mice with severe lung inflammation also displayed pronounced neutrophilia and anemia, characterized by increased granulopoiesis and decreased erythropoiesis in the bone marrow, compared to wild-type mice. This condition was associated with higher concentrations of granulocyte-colony stimulating factor (G-CSF) in both the lungs and serum, a factor known to enhance granulopoiesis. Neutrophils accumulating in the lungs of MPO^-/- mice produced greater amounts of G-CSF than those in wild-type mice, indicating that they are a significant source of G-CSF. <em>In vitro</em> experiments using signal transduction inhibitors and Western blot analysis revealed that MPO^-/- neutrophils express higher levels of G-CSF mRNA in response to Zymosan, attributed to the upregulation of the IκB kinase/nuclear factor (NF)-κB pathway and the extracellular-signal-regulated kinase/NF-κB pathway. These findings highlight MPO as a critical regulator of granulopoiesis and erythropoiesis in inflamed tissues.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 5","pages":"Article 152843"},"PeriodicalIF":2.5,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000615/pdfft?md5=b9c73231ec42a6172f07292fd3134f99&pid=1-s2.0-S0171298524000615-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142058020","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":"Dexmedetomidine induces IL-10 secretion by B lymphocytes in the peripheral blood of patients with hepatocellular carcinoma","authors":"Miaomiao Qin ,&nbsp;Yining Chen ,&nbsp;Xinxin Wang ,&nbsp;Xiaobao Zhang ,&nbsp;Xiongxiong Pan","doi":"10.1016/j.imbio.2024.152842","DOIUrl":"10.1016/j.imbio.2024.152842","url":null,"abstract":"<div><h3>Background/aim</h3><p>To investigate the distribution of subpopulations of peripheral blood B lymphocytes in individuals with hepatocellular carcinoma (HCC), and to evaluate the effect of dexmedetomidine (DEX) on B lymphocyte differentiation in patients with HCC in vitro.</p></div><div><h3>Methods</h3><p>Peripheral blood mononuclear cells (PBMCs) were collected from the HCC group and the healthy group, and the distribution of peripheral blood B-lymphocyte subpopulations in the two groups was examined by Flow Cytometry (FCM). B lymphocytes extracted from the peripheral blood of the HCC group were divided into D0, D1, D2 and D4 groups according to the different dose of DEX in the culture medium (0 μM, 1 μM, 2 μM and 4 μM). After 72 h of in vitro culture, FCM was used to detect differences in the percentage of apoptotic B lymphocytes and the percentage of B lymphocytes that can express interleukin 10(IL-10) and transforming growth factor-β (TGF-β) in each group.</p></div><div><h3>Results</h3><p>In contrast to the healthy group, the HCC group exhibited a statistically significant increase in the proportion of CD19 + CD73 + B lymphocyte subpopulation (P&lt;0.05). In the in vitro culture experiment, the differences in apoptosis of B lymphocytes and the percentage of TGF-β expression in each group were not statistically significant; When compared to the control group, there was a significant increase in the percentage of B lymphocytes expressing IL-10 across the D1, D2, and D4 groups (P&lt;0.05).</p></div><div><h3>Conclusion</h3><p>The peripheral blood of HCC patients is characterized by an elevated presence of CD19 + CD73 + B lymphocyte subpopulations; DEX may have an immunosuppressive effect by promoting IL-10 secretion from peripheral blood B lymphocytes of HCC patients.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 5","pages":"Article 152842"},"PeriodicalIF":2.5,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000603/pdfft?md5=9c402ab73f9d18329b994075cdbc52a7&pid=1-s2.0-S0171298524000603-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141998070","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":"TLR4/TNFR1 blockade suppresses STAT1/STAT3 expression and increases SOCS3 expression in modulation of LPS-induced macrophage responses","authors":"Ritasha Sawoo,&nbsp;Biswadev Bishayi","doi":"10.1016/j.imbio.2024.152840","DOIUrl":"10.1016/j.imbio.2024.152840","url":null,"abstract":"<div><p>Due to the urgent need to create appropriate treatment techniques, which are currently unavailable, LPS-induced sepsis has become a serious concern on a global scale. The primary active component in the pathophysiology of inflammatory diseases such as sepsis is the Gram-negative bacterial lipopolysaccharide (LPS). LPS interacts with cell surface TLR4 in macrophages, causing the formation of reactive oxygen species (ROS), TNF-α, IL-1β and oxidative stress. It also significantly activates the MAPKs and NF-κB pathway. Excessive production of pro-inflammatory cytokines is one of the primary characteristic features in the onset and progression of inflammation. Cytokines mainly signal through the JAK/STAT pathway. We hypothesize that blocking of TLR4 along with TNFR1 might be beneficial in suppressing the effects of STAT1/STAT3 due to the stimulation of SOCS3 proteins. Prior to the LPS challenge, the macrophages were treated with antibodies against TLR4 and TNFR1 either individually or in combination. On analysis of the macrophage populations by flowcytometry, it was seen that receptor blockade facilitated the phenotypic shift of the M1 macrophages towards M2 resulting in lowered oxidative stress. Blocking of TLR4/TNFR1 upregulated the SOCS3 and mTOR expressions that enabled the transition of inflammatory M1 macrophages towards the anti-inflammatory M2 phenotype, which might be crucial in curbing the inflammatory responses. Also the reduction in the production of inflammatory cytokines such as IL-6, IL-1β due to the reduction in the activation of the STAT1 and STAT3 molecules was observed in our combination treatment group. All these results indicated that neutralization of both TLR4 and TNFR1 might provide new insights in establishing an alternative therapeutic strategy for LPS-sepsis.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 5","pages":"Article 152840"},"PeriodicalIF":2.5,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000585/pdfft?md5=6fa21168b1f9f1a7014808462aaf447f&pid=1-s2.0-S0171298524000585-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141912445","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":"Integrated machine learning screened glutamine metabolism-associated biomarker SLC1A5 to predict immunotherapy response in hepatocellular carcinoma","authors":"Guixiong Zhang ,&nbsp;Yitai Xiao ,&nbsp;Hang Liu ,&nbsp;Yanqin Wu ,&nbsp;Miao Xue ,&nbsp;Jiaping Li","doi":"10.1016/j.imbio.2024.152841","DOIUrl":"10.1016/j.imbio.2024.152841","url":null,"abstract":"<div><p>Hepatocellular carcinoma (HCC) stands as one of the most prevalent malignancies. While PD-1 immune checkpoint inhibitors have demonstrated promising therapeutic efficacy in HCC, not all patients exhibit a favorable response to these treatments. Glutamine is a crucial immune cell regulatory factor, and tumor cells exhibit glutamine dependence. In this study, HCC patients were divided into two subtypes (C1 and C2) based on glutamine metabolism-related genes via consensus clustering. The C1 pattern, in contrast to C2, was associated with a lower survival probability among HCC patients. Additionally, the C1 pattern exhibited higher proportions of patients with advanced tumor stages. The activity of C1 in glutamine metabolism and transport is significantly enhanced, while its oxidative phosphorylation activity is reduced. And, C1 was mainly involved in the progression-related pathway of HCC. Furthermore, C1 exhibited high levels of immunosuppressive cells, cytokine-receptor interactions and immune checkpoint genes, suggesting C1 as an immunosuppressive subtype. After stepwise selection based on integrated four machine learning methods, SLC1A5 was finally identified as the pivotal gene that distinguishes the subtypes. The expression of SLC1A5 was significantly positively correlated with immunosuppressive status. SLC1A5 showed the most significant correlation with macrophage infiltration, and this correlation was confirmed through the RNA-seq data of CLCA project and our cohort. Low-SLC1A5-expression samples had better immunogenicity and responsiveness to immunotherapy. As expected, SubMap and survival analysis indicated that individuals with low SLC1A5 expression were more responsive to anti-PD1 therapy. Collectively, this study categorized HCC patients based on glutamine metabolism-related genes and proposed two subclasses with different clinical traits, biological behavior, and immune status. Machine learning was utilized to identify the hub gene SLC1A5 for HCC classification, which also could predict immunotherapy response.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 5","pages":"Article 152841"},"PeriodicalIF":2.5,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000597/pdfft?md5=9b728266aff2bc1d2b2340dc90eeaa7f&pid=1-s2.0-S0171298524000597-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141884016","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":"Selenium nanoparticles enhance the anti-tumor immune responses of anti-4-1BB antibody and alleviate the adverse effects on mice","authors":"Lei zhang ,&nbsp;Houru Liu ,&nbsp;Jie Shen ,&nbsp;Wenting Liu ,&nbsp;Dahai Liu ,&nbsp;Liansheng Cheng ,&nbsp;Bei Huang","doi":"10.1016/j.imbio.2024.152839","DOIUrl":"10.1016/j.imbio.2024.152839","url":null,"abstract":"<div><p>4-1BB agonists for cancer immunotherapy have shown good preliminary efficacy in clinical trials, but several of the first-generation 4-1BB agonistic antibodies entering the clinic have failed due to safety issues. Selenium nanoparticles (SeNPs) exhibit anti-inflammatory, anti-tumor, antioxidant, and immune-modulating properties. In addition, they have been shown to have detoxifying effects and prevent oxidative liver damage. In this study, we used an anti-4-1BB antibody in combination with SeNPs to evaluate the anti-lung cancer effects in <em>in vitro</em> and <em>in vivo</em> experiments and explore the underlying mechanisms by pathological analyses, quantitative PCR, and enzyme-linked immunoassay. We found that 5 μmol·L^–1 anti-4-1BB antibody combined with 1 μmol·L^–1 SeNPs increased the expression of IFN-γ and promoted the killing effects of peripheral blood mononuclear cells on Lewis lung carcinoma cells, with a lethality rate up to 56.88 %. Experiments in tumor-bearing mice showed that the tumor inhibition rate was 58.61 % after treatment with 3.5 mg/kg anti-4-1BB antibody combined with 0.25 mg/kg SeNPs, and the liver function index returned to normal. When the combined treatment was compared with the antibody treatment alone, detection of immune relevant factors demonstrated that the expression of FOXP3, IL-2, IL-12, and TNF-α in the spleen was downregulated, whereas the expression of IFN-γ in the spleen, serum, and tumor was upregulated, accompanied by increased Fas ligand expression in the tumor tissues. Based on these findings, we get the conclusion that anti-4-1BB antibody combined with SeNPs may alleviate the immunosuppression of regulatory T cells, promote the immune cell proliferation and metastasis to synergistically kill tumor cells. This combination also reduces the inflammatory damage to normal tissues and slows overstimulation of the splenic immune response.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 5","pages":"Article 152839"},"PeriodicalIF":2.5,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000573/pdfft?md5=e7ee470ed05e4a73e78719f7e0747e2e&pid=1-s2.0-S0171298524000573-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141878645","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":"In silico analysis of DEL-1 and inflammation-related genes in lung squamous cell carcinoma","authors":"Rahsan Ilikci-Sagkan ,&nbsp;Dilara Fatma Akin ,&nbsp;Recep Liman ,&nbsp;Muhammad Muddassir Ali","doi":"10.1016/j.imbio.2024.152838","DOIUrl":"10.1016/j.imbio.2024.152838","url":null,"abstract":"<div><h3>Aim</h3><p>Twenty to thirty percent of non-small cell lung cancers (NSCLC) are caused by lung squamous cell carcinoma (LUSC), especially in smokers and there has been limited study previously evaluating the situation in terms of the genome and gene expression profile, which demonstrates the relationship among DEL-1, leucocyte recruitment, and pro-inflammatory cytokines in LUSC.</p></div><div><h3>Material and methods</h3><p>In the current study, the m-RNA expression patterns and mutation profiles of our target genes, such as, pro-inflammatory cytokines, chemoattractant molecules, and DEL-1 genes, in 511 LUSC patients. To find the harmful mutations, the PolyPhen-2 and SNAP programs were employed. Not only gene expression was detected, but also survival analysis and correlation between DEL-1 and other target genes’ expression levels were explored too.</p></div><div><h3>Results</h3><p>Target genes such as, DEL-1, TNF, IL-18, IL-1, CXCL8, CXCL13, and IL-6 were found to have a total genetic anomaly carrying rate of 16.4%. Seven mutations were found, and two of those mutations have a pathogenic aspect. Deep deletion and gene amplification of the genetic anomalies were also observed. According to gene expression analysis results in the LUSC patient group; DEL-1 and IL-6 levels were significantly lower than those of the control group, whereas the CXCL13 level was found to be higher.</p></div><div><h3>Conclusion</h3><p>Findings of the current study revealed that, there is a significant role of DEL-1 in LUSC pathogenesis. Since present study is an <em>in silico</em>-centered study, this approach can give more insight on experimental studies. These events may support that one of the cancer improvement mechanisms depending on DEL-1 gene at the molecular level.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 5","pages":"Article 152838"},"PeriodicalIF":2.5,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000561/pdfft?md5=dd96604203daf8bde563dce322c58397&pid=1-s2.0-S0171298524000561-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141846902","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":"Synthetic hemozoin as a nanocarrier for cross-presentation","authors":"Letícia Torres-Dias ,&nbsp;Rebeca Santana Souza ,&nbsp;Jessica Carolina Alves Moreira ,&nbsp;Douglas de Oliveira Paggi ,&nbsp;Jônatas Bussador do Amaral ,&nbsp;André Luis Lacerda Bachi ,&nbsp;Leonardo Augusto ,&nbsp;Marina Tiemi Shio","doi":"10.1016/j.imbio.2024.152837","DOIUrl":"10.1016/j.imbio.2024.152837","url":null,"abstract":"<div><p>It is known that conventional antigen presentation involves phagocytosis of antigens followed by its internalization in endocytic compartments and presentation of epitopes through MHC class II molecules for CD4 T cells. However, since 1976 a cross-presentation pathway has been studied, in which CD8 T cells are activated via MHC class I with antigens acquired through phagocytosis or endocytosis by dendritic cells (DCs). Among some important molecules involved in the cross-presentation, the C‐type lectin receptor of the Dectin‐1 cluster (CLECs), particularly the CLEC9A receptor, not only is expressed in dendritic cells but also presents a pivotal role in this context. In special, CLEC12A has been highlighted as a malaria pigment hemozoin (HZ) receptor. During <em>Plasmodium</em> infection, hemozoin crystals defend the parasite against heme toxicity within erythrocytes, as well as the released native HZ elicits pro-inflammatory responses and can induce cross-presentation. Particularly, this crystal can be synthesized from hematin anhydride and mimics the native form, and the gaps generated between the nanocrystal domains during its synthesis allow for substance coupling followed by its coating. Therefore, this study aimed to assess whether synthetic hemozoin (sHz) or hematin anhydride could be a nanocarrier and promote cross-presentation in dendritic cells. Firstly, it was verified that sHz can carry coated and coupled antigens, the compounds can associate to LAMP1-positive vesicles and decrease overall intracellular pH, which can potentially enhance the cross-presentation of ovalbumin and <em>Leishmania infantum</em> antigens. Thus, this study adds important data in the molecular intricacies of antigen presentation by showing not only the sHz immunomodulatory properties but also its potential applications as an antigen carrier.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 5","pages":"Article 152837"},"PeriodicalIF":2.5,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S017129852400055X/pdfft?md5=87acf7e2346f18aa9f5541b48004b136&pid=1-s2.0-S017129852400055X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141841311","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}