Immunobiology最新文献

{"title":"Toll-like receptor expression and functional behavior in platelets from patients with systemic lupus erythematosus","authors":"María C. Baroni Pietto ,&nbsp;Ana C. Glembotsky ,&nbsp;Paola R. Lev ,&nbsp;Cecilia R. Marín Oyarzún ,&nbsp;Geraldine De Luca ,&nbsp;Graciela Gomez ,&nbsp;María V. Collado ,&nbsp;Nancy Charó ,&nbsp;Adela S. Cellucci ,&nbsp;Paula G. Heller ,&nbsp;Nora P. Goette ,&nbsp;Rosana F. Marta","doi":"10.1016/j.imbio.2023.152782","DOIUrl":"10.1016/j.imbio.2023.152782","url":null,"abstract":"<div><h3>Background</h3><p>Multiple blood cell abnormalities participate in the development of inflammation in systemic lupus erythematosus (SLE). Although platelets have been suggested as one of these contributors through the release of their content during activation, there are limited specific data about their role as immune players in SLE.</p></div><div><h3>Materials and Methods</h3><p>Thirteen SLE patients were included. Flow cytometry was used to measure Toll-like receptors (TLR) 2, 4, and 9 in resting platelets, platelet-activation markers (PAC-1 binding, P-selectin, CD63, and CD40 ligand -L) and platelet-leukocyte aggregates before and after specific TLR stimulation. Soluble CD40L and von Willebrand factor (vWf) release from stimulated platelets was measured using ELISA.</p></div><div><h3>Results</h3><p>In resting conditions, SLE platelets showed normal expression levels of TLR 2, 4 and 9. Platelet surface activation markers, soluble CD40L, and vWf release were normal at baseline and after TLR stimulation. Platelet-monocyte aggregates were elevated in resting conditions in SLE samples and showed only a marginal increase after TLR stimulation, while baseline and stimulated platelet-neutrophil and platelet-lymphocyte aggregates were normal. C-reactive protein levels positively correlated with platelet-monocyte aggregates both at baseline and after stimulation with the TLR-2 agonist PAM3CSK4, suggesting these complexes could reflect the inflammatory activity in SLE. In our cohort, 12 of 13 patients received treatment with hydroxychloroquine (HCQ), a known inhibitor of endosomal activity and a potential inhibitor of platelet activation. The fact that SLE platelets showed an adequate response to TLR agonists suggests that, despite this treatment, they retain the ability to respond to the increased levels of damage-associated molecular patterns (DAMPs), which represent known TLR ligands, present in the circulation of SLE patients. Interestingly, elevated plasma levels of high mobility group box 1 (HMGB1), a classical DAMP, correlated with vWf release from TLR-stimulated platelets, suggesting that HMGB1 may also be released by platelets, thereby creating a positive feedback loop for platelet activation that contributes to inflammation.</p></div><div><h3>Conclusion</h3><p>Our study demonstrates normal platelet TLR expression and function together with increased circulating platelet-monocyte aggregates. In addition, a direct correlation was observed between plasma HMGB1 levels and platelet vWf release following TLR2 stimulation. This platelet behavior in a group of patients undergoing HCQ treatment suggests that platelets could play a role in the inflammatory state of SLE.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 1","pages":"Article 152782"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298523045849/pdfft?md5=428b046d1f34f9ef58d2ae3616a538fb&pid=1-s2.0-S0171298523045849-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139051626","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":"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":"https://doi.org/10.1016/j.imbio.2023.152781","url":null,"abstract":"<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>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"11 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139028779","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":"ADAR1 regulates macrophage polarization and is protective against liver ischemia and reperfusion injury","authors":"Linxiao Wang ,&nbsp;Chujun Duan ,&nbsp;Xiuhua Wu ,&nbsp;Jiangang Xie ,&nbsp;Xiaojun Zhao ,&nbsp;Yi Si ,&nbsp;Dan Wu ,&nbsp;Yifan Wang ,&nbsp;Peng Zhao ,&nbsp;Jijun Chen ,&nbsp;Wen Yin ,&nbsp;Junjie Li","doi":"10.1016/j.imbio.2023.152777","DOIUrl":"10.1016/j.imbio.2023.152777","url":null,"abstract":"<div><p>Liver ischemia and reperfusion injury (LIRI) is a major risk for the poor prognosis of patients receiving liver transplantation. The molecular mechanism involved in LIRI is complex and related to various cellular components. We previously reported that adenosine deaminase acting on RNA 1 (ADAR1) alleviated the allogeneic skin graft rejection by regulating macrophage polarization. However, the regulatory effects of ADAR1 on liver macrophages after LIRI remain largely unknown. In this study, we mainly adopted a mouse model of LIRI and cellular experiments with hypoxia and reoxygenation (HR) treatment to explore the regulatory roles of ADAR1 on liver macrophages under LIRI conditions. We found that IRI caused decreased ADAR1 in liver tissues and remarkable changes of liver macrophage polarization and profiles. ADAR1 supplementation alleviated the pathological injury caused by IRI and accelerated the activation of M2 macrophages in the liver of IRI mice. Increased hypoxia duration reduced ADAR1 expression levels in murine RAW264.7 macrophages at the transcriptional level. Further overexpression of ADAR1 significantly increased the expressions of anti-inflammatory cytokines and promoted M2 polarization of macrophages under HR exposure. ADAR1 knockdown exhibited opposite effects on macrophage polarization. Hence, ADAR1 promotes the M2 polarization of liver macrophages that may further alleviate LIRI. The protective effects of ADAR1 against LIRI provide a novel insight into the prevention and treatment of LIRI.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 1","pages":"Article 152777"},"PeriodicalIF":2.8,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298523045795/pdfft?md5=a34f1199304f8318fb2dc83897551a8a&pid=1-s2.0-S0171298523045795-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138631730","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":"Chlorella vulgaris extract and Imiquimod as new therapeutic targets for leishmaniasis: An immunological approach","authors":"Maria Gabriella Nunes de Melo ,&nbsp;Isabelle Barreto da Silva Moreira Reino ,&nbsp;Victor Vaitkevicius-Antão ,&nbsp;Jady Moreira da Silva ,&nbsp;José Noé da Silva Júnior ,&nbsp;Alexsandra Frazão de Andrade ,&nbsp;Raquel Pedrosa Bezerra ,&nbsp;Daniela de Araújo Viana Marques ,&nbsp;Silvana de Fátima Ferreira da Silva ,&nbsp;Paulo Sérgio Ramos de Araújo ,&nbsp;Virginia Maria Barros de Lorena ,&nbsp;Rayana Carla Silva de Morais ,&nbsp;Milena de Paiva-Cavalcanti","doi":"10.1016/j.imbio.2023.152779","DOIUrl":"10.1016/j.imbio.2023.152779","url":null,"abstract":"<div><p>The therapeutic regimen for the treatment of American Tegumentary Leishmaniasis (ATL) is targeted at the death of the parasite; therefore, it is essential to develop a treatment that can act on the parasite, combined with the modulation of the inflammatory profile. Thus, the aim of this study was to make an <em>in vitro</em> evaluation of the therapeutic potential of <em>Chlorella vulgaris</em> extract (CV) and Imiquimod for ATL. Selectivity indices (SI) were determined by inhibitory concentration assays (IC₅₀) in <em>L</em>. <em>braziliensis</em> cells and cytotoxic concentrations (CC₅₀) were measured in human cells using the MTT method, based on the CV microalgae extract (IC₅₀ concentrations of 15.63 to 500 µg/mL; CC₅₀ concentrations of 62.5–1000 µg/mL) in comparison with the reference drugs and Imiquimod. The immune response was evaluated in healthy human cells by gene expression (RT-qPCR) and cytokine production (Flow Cytometry). The CV extract (SI = 6.89) indicated promising results by showing higher SI than meglumine antimoniate (SI = 3.44) (reference drug). In all analyses, CV presented a protective profile by stimulating the production of Th1 profile cytokines to a larger extent than the reference drugs. Imiquimod showed a high expression for Tbx21, GATA3, RORc and Foxp3 genes, with increased production only of the TNF cytokine. Therefore, the data highlight the natural extract and Imiquimod as strong therapeutic or adjuvant candidates against ATL, owing to modulation of immune response profiles, low toxicity in human cells and toxic action on the parasite.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 1","pages":"Article 152779"},"PeriodicalIF":2.8,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298523045813/pdfft?md5=1ba7d96e9ef7d01be83b646d18bd426f&pid=1-s2.0-S0171298523045813-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138631814","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":"Up-Regulation of scleral C5b-9 and Its regulation of the NLRP3 Inflammasome in a Form-Deprivation Myopia Mouse Model","authors":"Kang Xiao ,&nbsp;Zhengyu Chen ,&nbsp;Songqing He ,&nbsp;Qin Long","doi":"10.1016/j.imbio.2023.152776","DOIUrl":"10.1016/j.imbio.2023.152776","url":null,"abstract":"<div><h3>Background</h3><p>Myopia has become a major public health problem worldwide. Although the involvement of the complement system in myopia progression has been reported, the underlying mechanism has not been well established. In this study, we induced a form deprivation (FD) myopia mouse model to investigate the mechanisms.</p></div><div><h3>Methods</h3><p>Both C6-knockout (KO) and wild-type (WT) mice were divided into FD and normal control (NC) groups. The FD myopia was induced in the right eyes of 24-day-old mice using a translucent balloon for 4 weeks. The left eye remained untreated and served as self-control. NC group received no treatment. Refractive error and axial length were measured at baseline, 2 weeks, and 4 weeks later under normal visual, 4 weeks after FD. Scleral transcriptome sequencing analysis was performed in in FD mice. The scleral levels of C5b-9, NLRP3, Caspase-1, IL-1β, MMP-2, and collagen I were evaluated using immunohistochemistry.</p></div><div><h3>Results</h3><p>RNA-seq analysis showed 1058 differentially expressed genes. The GO analysis showed these genes were mainly related to the extracellular matrix, and immune response. The KEGG enrichment analysis showed that complement cascades were upregulated. Under normal visual conditions, both genotypes of mice exhibited comparable refractive error and axial length. However, after four weeks of FD, C6-KO mice showed a significantly less myopic shift (−2.28 ± 0.28 D versus −5.40 ± 1.33 D, <em>P</em> = 0.003), and axial shift (0.043 ± 0.032 mm versus 0.083 ± 0.026 mm, <em>P</em> = 0.042) in comparison to WT mice. Furthermore, the levels of C5b-9, NLRP3, caspase-1, IL-1β, and MMP-2 were found to be elevated in the deprived eyes of WT mice in comparison to their fellow eyes, whereas the extent of this increase was significantly lower in C6-KO mice.</p></div><div><h3>Conclusions</h3><p>Complement cascades are activated in FD myopia model. Upregulation of C5b-9 might participate in scleral remodeling during myopia progression via regulation of NLRP3 inflammasome activation.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 1","pages":"Article 152776"},"PeriodicalIF":2.8,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298523045783/pdfft?md5=1b7837a74a2206894e1eb8d04e3ba6b1&pid=1-s2.0-S0171298523045783-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138573254","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":"Vitexin along with verapamil downregulates efflux pump P-glycoprotein in macrophages and potentiate M1 to M2 switching via TLR4-NF-κB-TNFR2 pathway in lipopolysaccharide treated mice","authors":"Ayantika Kundu,&nbsp;Pratiti Ghosh ,&nbsp;Biswadev Bishayi","doi":"10.1016/j.imbio.2023.152767","DOIUrl":"10.1016/j.imbio.2023.152767","url":null,"abstract":"<div><p>The lipopolysaccharide, a microbial toxin, is one of the major causative agents of sepsis. P-gp expression and its functions are altered during inflammation. LPS has been known to impair the functions of P-gp, an efflux transporter. But the effect of LPS on P-gp expression in murine peritoneal macrophages is poorly understood. Molecular docking studies reveal that vitexin is a potent substrate and verapamil a potent inhibitor of P-gp. In the present experimental study, the curative potential of vitexin as a fruit component and verapamil treated as a control inhibitor of P-gp was examined in a murine LPS sepsis model. The effects of vitexin and verapamil on P-gp expression in macrophages correlating with changes in macrophage polarization and associated functional responses during LPS induced sepsis were studied. Peritoneal macrophages of LPS (10 mg/kg body weight) challenged mice exhibited elevated levels of H₂O₂, superoxide, and NO in parallel with lower antioxidant activity. LPS treatment increased P-gp expression through increased TLR4/expression. However, LPS challenged mice treated with vitexin (5 mg/kg body weight) + verapamil (5 mg/kg body weight) showed higher anti-oxidant enzyme activity (SOD, CAT and GRx) resulting in reduced oxidative stress. This combination treatment also elevated TNFR2, concomitant with down-regulation of TLR4, NF-κB and P-gp expression in murine peritoneal macrophages, resulting in a switch from M1 to M2 polarisation of macrophages and reduced inflammatory responses. In conclusion, combined vitexin and verapamil treatment could be used as a promising therapy to regulate P-gp expression and protection against LPS mediated sepsis and inflammatory damages.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 1","pages":"Article 152767"},"PeriodicalIF":2.8,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298523045692/pdfft?md5=f258a2275276a3345924fb357bc439d2&pid=1-s2.0-S0171298523045692-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138520274","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":"Alteration of PBMC transcriptome profile after interaction with multipotent mesenchymal stromal cells under “physiological” hypoxia","authors":"A.N. Gornostaeva ,&nbsp;P.I. Bobyleva ,&nbsp;E.R. Andreeva ,&nbsp;B.Sh. Gogiya ,&nbsp;L.B. Buravkova","doi":"10.1016/j.imbio.2023.152766","DOIUrl":"https://doi.org/10.1016/j.imbio.2023.152766","url":null,"abstract":"<div><p>Multipotent mesenchymal stromal cells (MSCs) have demonstrated a pronounced immunosuppressive activity, the manifestation of which depends on the microenvironmental factors, including O₂ level.</p><p>Here we examined the effects of MSCs on transcriptomic profile of allogeneic phytohemagglutinin-stimulated peripheral blood mononuclear cells (PBMCs) after interaction at ambient (20%) or “physiological” hypoxia (5%) O₂. As revealed with microarray analysis, PBMC transcriptome at 20% O₂ was more affected, which was manifested as differential expression of more than 300 genes, whereas under 5% O₂ 220 genes were changed. Most of genes at 20% O₂ were downregulated, while at hypoxia most of genes were upregulated. Altered gene patterns were only partly overlapped at different O₂ levels. A set of altered genes at hypoxia only was of particular interest. According to Gene Ontology a part of above genes was responsible for adhesion, cell communication, and immune response. At both oxygen concentrations, MSCs demonstrated effective immunosuppression manifested as attenuation of T cell activation and proliferation as well as anti-inflammatory shift of cytokine profile.</p><p>Thus, MSC-mediated immunosuppression is executed with greater efficacy at a “physiological” hypoxia, since the same result has been achieved through a change in the expression of a fewer genes in target PBMCs.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 1","pages":"Article 152766"},"PeriodicalIF":2.8,"publicationDate":"2023-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298523045680/pdfft?md5=4f8bae269ebf6ebbece4914aa4a559a4&pid=1-s2.0-S0171298523045680-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138570156","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":"The signature and predictive value of immune parameters in patients with secondary hemophagocytic lymphohistiocytosis","authors":"Huan Bai ,&nbsp;Yun Wang ,&nbsp;Ling Shen ,&nbsp;Ying Luo ,&nbsp;Guoxing Tang ,&nbsp;Feng Wang ,&nbsp;Ziyong Sun ,&nbsp;Hongyan Hou","doi":"10.1016/j.imbio.2023.152759","DOIUrl":"10.1016/j.imbio.2023.152759","url":null,"abstract":"<div><h3>Background</h3><p>Secondary hemophagocytic lymphohistiocytosis (sHLH) is a rare but fatal clinical syndrome, characterized by severe immune dysfunction and overwhelming inflammatory response. However, the host immune signature and also its role in predicting the clinical outcome are not fully described.</p></div><div><h3>Objective</h3><p>The present study aims to investigate the host immune status of sHLH patients in the early stage of the disease, including lymphocyte subsets, phenotypes and cytokines, and also to explore its clinical value in prognosis.</p></div><div><h3>Methods</h3><p>Sixty-four patients with sHLH admitted to a tertiary hospital in central China between 2018 and 2022 were enrolled, of which 21 were deceased. The subsets and phenotypes of lymphocytes, and the levels of cytokines in serum were analyzed.</p></div><div><h3>Results</h3><p>In patients with sHLH, the percentages of total T cells, CD8⁺ T cells, HLA-DR⁺ T cells, HLA-DR⁺CD8⁺ T cells, CD45RO⁺CD4⁺ T cells, and the levels of IL-1β, IL-2R, IL-6, IL-8, IL-10 and TNF-α were significantly increased, while the percentages of CD4⁺ T cells, NK cells, CD45RA⁺CD4⁺ T cells, CD45RA⁺ regulatory T (Treg) cells, the counts of total T cells, total B cells, CD4⁺ T cells, CD8⁺ T cells, NK cells, and the ratio of CD4⁺ T/CD8⁺ T cells were significantly decreased, compared with healthy controls (HC). In addition, dysregulation of host immune response and high inflammatory status were more obvious in deceased patients than that of survivors. Kaplan-Meier survival analysis and multivariate logistic regression analysis demonstrated that lower levels of CD4⁺ T cells count and CD28⁺CD4⁺ T cells percentage, but higher levels of NK cells percentage and IL-1β were poor prognostic indicators of sHLH.</p></div><div><h3>Conclusion</h3><p>The evaluation of immunological markers has critical value for selecting prognostic markers and potential treatment target among adults with sHLH.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"228 6","pages":"Article 152759"},"PeriodicalIF":2.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71521324","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":"Comparable cytokine release ex-vivo by whole blood from COVID-19 patients with and without non-invasive ventilation","authors":"Martina Bonacini ,&nbsp;Ilaria Ferrigno ,&nbsp;Alessandro Rossi ,&nbsp;Nicola Facciolongo ,&nbsp;Marco Massari ,&nbsp;Romina Corsini ,&nbsp;Veronica Galli ,&nbsp;Alessandro Zerbini ,&nbsp;Carlo Salvarani ,&nbsp;Stefania Croci","doi":"10.1016/j.imbio.2023.152755","DOIUrl":"https://doi.org/10.1016/j.imbio.2023.152755","url":null,"abstract":"<div><p>T cells are key players in the resolution of the infection by SARS-CoV-2. A delay in their activation can lead to severe COVID-19. The present work aimed to identify differences in cytokine release by T cells <em>ex-vivo</em> between COVID-19 patients in the acute phase, showing diverse disease severity. Concentrations of IFNγ, Granzyme B, IL-6, IL-10, IL-17A, IL-18, IP-10, MCP-1, and TNFα were evaluated after stimulation <em>ex-vivo</em> of whole blood samples with peptides from SARS-CoV-2 spike protein and a mitogen as well as without stimulation. Samples derived from hospitalized COVID-19 patients and SARS-CoV-2 vaccinated controls (CTR). Patients were classified on disease severity considering the necessity of non-invasive ventilation (NIV). Samples from patients requiring NIV revealed a similar release of cytokines compared with patients without NIV. COVID-19 patients showed higher spontaneous production of IFNγ and IP-10, lower production of MCP-1 after SARS-CoV-2 peptide stimulation and lower production of IFNγ, IL-10, IL-17A, Granzyme B, IP-10 after mitogenic stimulus compared with CTR. In conclusion, differences in T cell responses evaluated <em>ex-vivo</em> by a whole blood-based cytokine release assay do not appear to explain the need for non-invasive ventilation in COVID-19 patients.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"228 6","pages":"Article 152755"},"PeriodicalIF":2.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92037517","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":"PLEKHA4 promotes glioblastoma progression through apoptosis inhibition, tumor cell migration, and macrophage infiltration","authors":"Yang He ,&nbsp;Wenjing Zheng ,&nbsp;Yi Huo ,&nbsp;Longqi Sa ,&nbsp;Han Zhang ,&nbsp;Guangbin He ,&nbsp;Panfeng Shang","doi":"10.1016/j.imbio.2023.152746","DOIUrl":"10.1016/j.imbio.2023.152746","url":null,"abstract":"<div><h3>Background</h3><p>Glioblastoma(GBM) has a profound impact on human health<span>, making the identification of reliable prognostic biomarkers pivotal. While PLEKHA4 has been associated with tumor genesis and development, its role in gliomas is still uncertain.</span></p></div><div><h3>Methods</h3><p>We analyzed PLEKHA4 expression in tumor tissues using the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus<span> (GEO) databases. Additionally, we utilized TCGA data to investigate its impact on prognosis, pathway enrichment, and immune infiltration. In vitro loss-of-function experiments were conducted to elucidate the effect of PLEKHA4 silencing on GBM cell behavior.</span></p></div><div><h3>Results</h3><p>TCGA and GEO data sets revealed increased levels of PLEKHA4 expression in glioma tissues. Furthermore, we identified a correlation between PLEKHA4 expression and higher disease classification<span><span>, pathological grading, and poorer prognosis. Silencing PLEKHA4 in vitro resulted in decreased glioma cell migration and increased </span>apoptosis. It also reduced macrophage infiltration and hindered M2 polarization of macrophages.</span></p></div><div><h3>Conclusion</h3><p>Our findings highlight the pivotal role of PLEKHA4 in GBM pathogenesis and suggest its potential as a diagnostic and therapeutic target for GBM.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"228 6","pages":"Article 152746"},"PeriodicalIF":2.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135389338","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}