Liting Ji, Gang Liu, Gongmin Yu, Changxing Xia, Shan Liu, Yunping Lan
{"title":"Resolvin E1 and Inhibition of BLT2 Signaling Attenuate the Inflammatory Response and Improve One-Lung Ventilation-Induced Lung Injury.","authors":"Liting Ji, Gang Liu, Gongmin Yu, Changxing Xia, Shan Liu, Yunping Lan","doi":"10.1080/08820139.2024.2399587","DOIUrl":"10.1080/08820139.2024.2399587","url":null,"abstract":"<p><strong>Introduction: </strong>One-lung ventilation (OLV) is a prevalently used technique to sustain intraoperative pulmonary function. Resolvin E1 (RvE1), a specialized pro-resolving lipid mediator, accelerates the resolution of inflammation in the lungs. However, its therapeutic effects on OLV-induced lung injury remain unclear.</p><p><strong>Methods: </strong>We initially developed an OLV rat model and treated it with RvE1. Subsequently, we assessed the wet/dry ratio of the lung tissue, performed hematoxylin and eosin staining, and calculated the ratio of polymorphonuclear cells to white blood cells in the bronchoalveolar lavage fluid. Additionally, we assessed apoptosis, inflammatory factor levels, and lung permeability in the rat lung tissues in the RvE1 treated and untreated groups and explored the molecular mechanisms mediated by RvE1.</p><p><strong>Results: </strong>Our results indicated that RvE1 alleviated lung injury and inflammation and improved lung tissue apoptosis and permeability in OLV rats. Moreover, RvE1 suppressed the expression of the BLT1/2 signaling pathway and its ligands. The use of BLT2 and BLT1 inhibitors (LY255283 and U-75302, respectively) enhanced RvE1's anti-inflammatory effects and reduced lung injury. Furthermore, synergistic treatment with the BLT2 inhibitor and RvE1 provided grater benefits by more effectively inhibiting the NF-kB, p38 MAPK, and ERK pathways.</p><p><strong>Discussion: </strong>RvE1 and the inhibition of BLT2 signalling reduce the inflammatory response and mitigate OLV-induced lung injury. These findings suggest a novel therapeutic pathway for managing OLV-related complications.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"1293-1307"},"PeriodicalIF":2.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125628","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":"Genome-Wide Identification of Cell Type-Specific Susceptibility Genes for SLE Through the Analysis of RNA Modification-Associated SNPs.","authors":"Huan Zhang, Kedi Fan, Yuxi Chen, Peng Xu, Zhentao Zhang, Xingbo Mo, Yufan Guo","doi":"10.1080/08820139.2024.2399577","DOIUrl":"10.1080/08820139.2024.2399577","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to elucidate the functional genes associated with systemic lupus erythematosus (SLE) in various cell types through the utilization of RNAm-SNPs.</p><p><strong>Methods: </strong>Utilizing large-scale genetic data, we identified associations between RNAm-SNPs and SLE. The association between RNAm-SNPs and bulk and single-cell mRNA expression (eQTL) and protein levels (pQTL) were examined. Mendelian randomization and differential expression analyses were conducted to explore the links between gene expression, protein levels, and SLE.</p><p><strong>Results: </strong>We identified 41 RNAm-SNPs that were significantly associated with SLE. The GWAS signals exhibited notable enrichment in m<sup>6</sup>A-SNPs and m<sup>7</sup>G-SNPs. These RNAm-SNPs showed both eQTL and pQTL effects. In our single-cell analysis, 16 RNAm-SNPs exhibited associations with gene expression levels across 13 distinct cell types, including <i>HLA-A, HLA-B, HLA-C, HLA-DQA1, HLA-DQB1, HLA-DRB1</i> and <i>IRF7</i>. We identified 58 noteworthy associations between the expression levels of 20 genes and SLE across 12 distinct immune cell types. Notably, <i>HLA-DQB1, HLA-DRB1</i> and <i>IRF7</i> exhibited abnormalities in CD8+ T cells, <i>IRF7</i> displayed abnormal expression in CD4+ T cells, while <i>HLA-DRB1</i> and <i>IRF7</i> were also distinctly perturbed in natural killer cells.</p><p><strong>Discussion: </strong>This study advances our understanding of the genetic basis of SLE by highlighting the significance of RNAm-SNPs and immune cell gene expression in SLE.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"1264-1278"},"PeriodicalIF":2.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125627","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":"Correlation and Clinical Significance of HBD-2 and CXCL-1/2 Levels at Skin Lesions with Psoriasis Vulgaris Severity.","authors":"Ling Lin, Quan Luo, Xinjing Gao, Qian Li, Wei Li, Xin Zhou, Weiyu Liu, Xuelian Zhong, Yunqing Yang, Xibao Zhang","doi":"10.1080/08820139.2024.2395852","DOIUrl":"10.1080/08820139.2024.2395852","url":null,"abstract":"<p><strong>Objective: </strong>This study was performed to explore the clinical significance of the expression of human beta-defensin 2 (HBD-2) and chemokine ligand 1/2 (CXCL-1/2) in psoriasis vulgaris.</p><p><strong>Methods: </strong>This study retrospectively included the study group (n = 160) and control group (n = 100) for analysis. The levels of inflammatory indicators, blood biochemical indicators, and immune indicators using ELISA. The psoriasis area and severity index (PASI) was used to evaluate disease severity. Levels of HBD-2, CXCL-1, CXCL-2 and CCL20 were determined by RT-PCR. The correlations of HBD-2, CXCL-1 and CXCL-2 levels with CCL20 and PASI scores were analyzed. The diagnostic value of HBD-2, CXCL-1 and CXCL-2 in psoriasis vulgaris was analyzed by ROC curve.</p><p><strong>Results: </strong>HBD-2, CXCL-1 and CXCL-2 were highly expressed in the lesions of psoriasis vulgaris patients, and were positively correlated with CCL20 and PASI score. HBD-2, CXCL-1 and CXCL-2 alone or in combination had high diagnostic value for psoriasis vulgaris and severe psoriasis, and the combined diagnostic value of the three was higher than that of a single indicator.</p><p><strong>Conclusion: </strong>HBD-2, CXCL-1, and CXCL-2 levels are closely related to the severity of psoriasis vulgaris and can effectively diagnose the occurrence and progression of psoriasis vulgaris.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"1234-1249"},"PeriodicalIF":2.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286169","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":"Crosstalk and Prospects of TBK1 in Inflammation.","authors":"Huan Liu, Qihuan Sheng, Juhua Dan, Xiaoli Xie","doi":"10.1080/08820139.2024.2392587","DOIUrl":"10.1080/08820139.2024.2392587","url":null,"abstract":"<p><strong>Background: </strong>TANK-binding kinase 1 (TBK1) is a pivotal mediator of innate immunity, activated by receptors such as mitochondrial antiviral signaling protein (MAVS), stimulator of interferon genes (STING), and TIR-domain-containing adaptor inducing interferon-β (TRIF). It modulates immune responses by exerting influence on the type I interferons (IFN-Is) signaling and the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways, Over the past few years, TBK1 multifaceted role in both immune and inflammatory responses is increasingly recognized.</p><p><strong>Methods and results: </strong>This review aims to scrutinize how TBK1 operates within the NF-κB pathway and the interferon regulatory transcription factor 3 (IRF3)-dependent IFN-I pathways, highlighting the kinases and other molecules involved in these processes. This analysis reveals the distinctive characteristics of TBK1's involvement in these pathways. Furthermore, it has been observed that the role of TBK1 in exerting anti-inflammatory or pro-inflammatory effects is contingent upon varying pathological conditions, indicating a multifaceted role in immune regulation.</p><p><strong>Discussion: </strong>TBK1's evolving role in various diseases and the potential of TBK1 inhibitors as therapeutic agents are explored. Targeting TBK1 may provide new strategies for treating inflammatory disorders and autoimmune diseases associated with IFN-Is, warranting further investigation.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"1205-1233"},"PeriodicalIF":2.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080190","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":"Characteristics of T-Cell Receptor Repertoire for Differential Response to Methotrexate Treatment for Rheumatoid Arthritis.","authors":"Taowa Zhao, Qian Zhang, Qinwen Wen, Shuyin Liu, Zitong Niu, Yang Qu, Yiting Wang, Qiaojiao Ding, Pengyao Wei, Lin Li, Tong Kong, Pan Fu, Sihua Qian, Kaizhe Wang, Xiudi Wu, Jianping Zheng","doi":"10.1080/08820139.2024.2381078","DOIUrl":"10.1080/08820139.2024.2381078","url":null,"abstract":"<p><strong>Background: </strong>Methotrexate (MTX) serves as the initial treatment for rheumatoid arthritis (RA). However, a substantial proportion of RA patients, estimated between 30% and 50%, do not respond positively to MTX. While the T-cell receptor (TCR) is crucial for the immune response during RA, its role in differentiating MTX responsiveness has not been thoroughly investigated.</p><p><strong>Methods: </strong>This study used next-generation sequencing to analyze the TCR β-chain complementary determining region sequences in peripheral blood mononuclear cells obtained from RA patients before MTX treatment. This study aimed to compare the characteristics of the TCR repertoire between the MTX responder and non-responder groups.</p><p><strong>Results: </strong>The study identified a significant difference in the TRBV6-6 gene (<i>p</i> = .003) concerning MTX treatment response. Additionally, a significant difference was found in the number of \"3\" nucleotide deletions at the 5'Jdels site (<i>p</i> = .023) in the VDJ rearrangement.</p><p><strong>Conclusion: </strong>These findings suggest distinct TCR repertoire characteristics between MTX responder and non-responder groups among RA patients. This discovery offers new insights into understanding the variable responses of RA patients to MTX therapy.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"1113-1124"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975615","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}
Abby M Luu, Kelly M Shepardson, Agnieszka Rynda-Apple
{"title":"A Comprehensive Protocol for the Collection, Differentiation, Cryopreservation, and Resuscitation of Primary Murine Bone Marrow Derived Macrophages (BMDM).","authors":"Abby M Luu, Kelly M Shepardson, Agnieszka Rynda-Apple","doi":"10.1080/08820139.2024.2382805","DOIUrl":"10.1080/08820139.2024.2382805","url":null,"abstract":"<p><strong>Background: </strong>The field of immunology has undoubtedly benefited from the <i>in vitro</i> use of cell lines for immunological studies; however, due to the \"immortal\" nature of many cell lines, they are not always the best model. Thus, direct collection and culture of primary cells from model organisms is a solution that many researchers utilize. To the best of our knowledge, there is not a singular protocol which encompasses the entire process of bone marrow cell collection through cryopreservation and resuscitation of cells from a murine model.</p><p><strong>Methods: </strong>Bone marrow cells were collected from mice with a C57BL6 genetic background. Cells were differentiated using L929 conditioned media. Cells were assessed using a combination of microscopy, differential staining, immunocytochemistry, and trypan blue. Results: Primary murine BMDMs that underwent cryopreservation followed by resuscitation retained a high degree of viability. Furthermore, these BMDMs retained on overall ability to clear <i>S. aureus</i>.</p><p><strong>Results: </strong>Primary murine BMDMs that underwent cryopreservation followed by resuscitation retained a high degree of viability. Furthermore, these BMDMs retained on overall ability to clear <i>S. aureus</i>.</p><p><strong>Conclusion: </strong>Crypopreserved and resuscitated primary murine BMDMs were viable and retained their pverall <i>S. aureus</i> clearance ability.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"1001-1012"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11451725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901602","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}
Rephany Fonseca Peixoto, Pedro Henrique de Sousa Palmeira, Bárbara Guimarães Csordas, Luiz Henrique Agra Cavalcante-Silva, Arthur Gomes de Andrade, Isac Almeida de Medeiros, Fátima de Lourdes Assunção Araújo de Azevedo, Robson Cavalcante Veras, Daniele Janebro, Ian P G Do Amaral, Tatjana Souza Lima Keesen
{"title":"Predominance of CD137<sup>+</sup> And TNF-α Expressing CD8<sup>+</sup> Central Memory T Cells in Mild COVID-19 Recovered Patients Upon SARS-CoV-2 Re-Exposure.","authors":"Rephany Fonseca Peixoto, Pedro Henrique de Sousa Palmeira, Bárbara Guimarães Csordas, Luiz Henrique Agra Cavalcante-Silva, Arthur Gomes de Andrade, Isac Almeida de Medeiros, Fátima de Lourdes Assunção Araújo de Azevedo, Robson Cavalcante Veras, Daniele Janebro, Ian P G Do Amaral, Tatjana Souza Lima Keesen","doi":"10.1080/08820139.2024.2376003","DOIUrl":"10.1080/08820139.2024.2376003","url":null,"abstract":"<p><strong>Introduction: </strong>Memory CD8<sup>+</sup> T cells are essential for long-term immune protection in viral infections, including COVID-19.</p><p><strong>Methods: </strong>This study examined the responses of CD8<sup>+</sup> TEM, TEMRA, and TCM subsets from unvaccinated individuals who had recovered from mild and severe COVID-19 by flow cytometry.</p><p><strong>Results and discussion: </strong>The peptides triggered a higher frequency of CD8<sup>+</sup> TCM cells in the recovered mild group. CD8<sup>+</sup> TCM and TEM cells showed heterogeneity in CD137 expression between evaluated groups. In addition, a predominance of CD137 expression in naïve CD8<sup>+</sup> T cells, TCM, and TEM was observed in the mild recovered group when stimulated with peptides. Furthermore, CD8<sup>+</sup> TCM and TEM cell subsets from mild recovered volunteers had higher TNF-α expression. In contrast, the expression partner of IFN-γ, IL-10, and IL-17 indicated an antiviral signature by CD8<sup>+</sup> TEMRA cells. These findings underscore the distinct functional capabilities of each memory T cell subset in individuals who have recovered from COVID-19 upon re-exposure to SARS-CoV-2 antigens.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"1092-1101"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590211","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":"The Role of Neuro-Immune Interactions in the Pathology and Pathogenesis of Allergic Rhinitis.","authors":"Ya-An Lan, Jia-Xi Guo, Min-Hua Yao, Yi-Ting Kang, Zi-Rui Liao, Yu-Hong Jing","doi":"10.1080/08820139.2024.2382792","DOIUrl":"10.1080/08820139.2024.2382792","url":null,"abstract":"<p><strong>Background: </strong>Allergic rhinitis (AR) is a non-infectious inflammatory disease of the nasal mucosa mediated by IgE and involving a variety of immune cells such as mast cells. In previous studies, AR was considered as an isolated disease of the immune system. However, recent studies have found that the nervous system is closely related to the development of AR. Bidirectional communication between the nervous and immune systems plays an important role in AR.</p><p><strong>Summary: </strong>The nervous system and immune system depend on the anatomical relationship between nerve fibers and immune cells, as well as various neurotransmitters, cytokines, inflammatory mediators, etc. to produce bidirectional connections, which affect the development of AR.</p><p><strong>Key messages: </strong>This article reviews the impact of neuro-immune interactions in AR on the development of AR, including neuro-immune cell units.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"1013-1029"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748109","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":"Targeting Macrophage Polarization in Infectious Diseases: M1/M2 Functional Profiles, Immune Signaling and Microbial Virulence Factors.","authors":"Cláudio Daniel Cerdeira, Maísa R P L Brigagão","doi":"10.1080/08820139.2024.2367682","DOIUrl":"10.1080/08820139.2024.2367682","url":null,"abstract":"<p><strong>Introduction: </strong>An event of increasing interest during host-pathogen interactions is the polarization of patrolling/naive monocytes (MOs) into macrophage subsets (MФs). Therapeutic strategies aimed at modulating this event are under investigation.</p><p><strong>Methods: </strong>This review focuses on the mechanisms of induction/development and profile of MФs polarized toward classically proinflammatory (M1) or alternatively anti-inflammatory (M2) phenotypes in response to bacteria, fungi, parasites, and viruses.</p><p><strong>Results and discussion: </strong>It highlights nuclear, cytoplasmic, and cell surface receptors (pattern recognition receptors/PPRs), microenvironmental mediators, and immune signaling. MФs polarize into phenotypes: M1 MФs, activated by IFN-γ, pathogen-associated molecular patterns (PAMPs, e.g. lipopolysaccharide) and membrane-bound PPRs ligands (TLRs/CLRs ligands); or M2 MФs, induced by interleukins (ILs-4, -10 and -13), antigen-antibody complexes, and helminth PAMPs. Polarization toward M1 and M2 profiles evolve in a pathogen-specific manner, with or without canonicity, and can vary widely. Ultimately, this can result in varying degrees of host protection or more severe disease outcome. On the one hand, the host is driving effective MФs polarization (M1 or M2); but on the other hand, microorganisms may skew the polarization through virulence factors to increase pathogenicity. Cellular/genomic reprogramming also ensures plasticity of M1/M2 phenotypes. Because modulation of polarization can occur at multiple points, new insights and emerging perspectives may have clinical implications during the inflammation-to-resolution transition; translated into practical applications as for therapeutic/vaccine design target to boost microbicidal response (M1, e.g. triggering oxidative burst) with specifics PAMPs/IFN-γ or promote tissue repair (M2, increasing arginase activity) via immunotherapy.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"1030-1091"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446054","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}
Pınar Gur Cetinkaya, Irem Fatma Abras, Irem Evcili, Tugçe Yildirim, Yasemin Ceylan, Fehime Kara Eroglu, Başak Kayaoglu, Emre Mert İpekoglu, Aysegul Akarsu, Muzaffer Yıldırım, Tamer Kahraman, Ali Bülent Cengiz, Umit Murat Sahiner, Bulent Enis Sekerel, Yasemin Ozsurekci, Ozge Soyer, Ihsan Gursel
{"title":"Plasma Extracellular Vesicles Derived from Pediatric COVID-19 Patients Modulate Monocyte and T Cell Immune Responses Based on Disease Severity.","authors":"Pınar Gur Cetinkaya, Irem Fatma Abras, Irem Evcili, Tugçe Yildirim, Yasemin Ceylan, Fehime Kara Eroglu, Başak Kayaoglu, Emre Mert İpekoglu, Aysegul Akarsu, Muzaffer Yıldırım, Tamer Kahraman, Ali Bülent Cengiz, Umit Murat Sahiner, Bulent Enis Sekerel, Yasemin Ozsurekci, Ozge Soyer, Ihsan Gursel","doi":"10.1080/08820139.2024.2385992","DOIUrl":"10.1080/08820139.2024.2385992","url":null,"abstract":"<p><strong>Background: </strong>The COVID-19 pandemic has caused significant morbidity and mortality globally. The role of plasma-derived extracellular vesicles (EVs) in pediatric COVID-19 patients remains unclear.</p><p><strong>Methods: </strong>We isolated EVs from healthy controls (n = 13) and pediatric COVID-19 patients (n = 104) with varying severity during acute and convalescent phases using serial ultracentrifugation. EV effects on healthy PBMCs, naïve CD4+ T cells, and monocytes were assessed through in vitro assays, flow cytometry, and ELISA.</p><p><strong>Results: </strong>Our findings indicate that COVID-19 severity correlates with diverse immune responses. Severe acute cases exhibited increased cytokine levels, decreased IFNγ levels, and lower CD4+ T cell and monocyte counts, suggesting immunosuppression. EVs from severe acute patients stimulated healthy cells to express higher PDL1, increased Th2 and Treg cells, reduced IFNγ secretion, and altered Th1/Th17 ratios. Patient-derived EVs significantly reduced proinflammatory cytokine production by monocytes (p < .001 for mild, p = .0025 for severe cases) and decreased CD4+ T cell (p = .043) and monocyte (p = .033) populations in stimulated healthy PBMCs.</p><p><strong>Conclusion: </strong>This study reveals the complex relationship between immunological responses and EV-mediated effects, emphasizing the impact of COVID-19 severity. We highlight the potential role of plasma-derived EVs in early-stage immunosuppression in severe COVID-19 patients.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"1141-1175"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901529","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}