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Diagnostic Significance of Metagenomic Next-Generation Sequencing in Immunocompromised Patients With Suspected Pulmonary Infection 新一代宏基因组测序在疑似肺部感染的免疫功能低下患者中的诊断意义。
IF 4.9 3区 医学
Immunology Pub Date : 2025-02-23 DOI: 10.1111/imm.13911
Xi Zheng, Wei Zou, Shumei Zou, Jia Ye, Zhenming Bao, Yingfang Song
{"title":"Diagnostic Significance of Metagenomic Next-Generation Sequencing in Immunocompromised Patients With Suspected Pulmonary Infection","authors":"Xi Zheng,&nbsp;Wei Zou,&nbsp;Shumei Zou,&nbsp;Jia Ye,&nbsp;Zhenming Bao,&nbsp;Yingfang Song","doi":"10.1111/imm.13911","DOIUrl":"10.1111/imm.13911","url":null,"abstract":"<p>Immunocompromised hosts are highly vulnerable to lung infections, but the efficacy of traditional diagnosis is unsatisfactory. Metagenomic next-generation sequencing (mNGS) has high throughput and broad coverage. Its value in different types of immunocompromised patients has yet to be fully explored. Therefore, the study aims to evaluate the value of mNGS in immunocompromised patients. Clinical data from immunocompromised patients with suspected pulmonary infection (PI) (September 2018–2021) were retrospectively analysed. Patients were categorised into PI (87 cases) and non-pulmonary infection (NPI, 14 cases) groups. The diagnostic performance between mNGS and conventional microbiological tests (CMTs) was compared. Subgroup analyses were also conducted based on whether the patients received organ transplantation, including the comparison of the diagnostic performance of mNGS and culture and the spectrum of characteristics among them. mNGS demonstrated significantly elevated diagnostic sensitivity (<i>p</i> &lt; 0.001) over traditional methods, with a pronounced advantage in identifying mixed PIs (<i>p</i> &lt; 0.05). Among immunocompromised cohorts, mNGS outperformed cultures, showing higher positivity rates in both organ transplant (<i>p</i> &lt; 0.001) and non-transplant patients (<i>p</i> &lt; 0.001). Mixed infections, predominantly bacterial–fungal, were more prevalent in transplant recipients with reduced lymphocytes and CD4<sup>+</sup> T cells. Pathogen profiles differed, with <i>Pneumocystis jirovecii</i>, <i>Cytomegalovirus</i>, and \u0000 <i>Pseudomonas aeruginosa</i>\u0000 predominating in organ transplant recipients, and <i>P. jirovecii</i>, \u0000 <i>P. aeruginosa</i>\u0000 , \u0000 <i>Streptococcus pneumoniae</i>\u0000 and <i>Streptococcus pallidum</i> in non-transplant individuals. mNGS is valuable in diagnosing PI and mixed infections in immunocompromised patients, which may be particularly suitable for identifying mixed infections in patients with organ transplants and low lymphocyte and CD4<sup>+</sup> T lymphocyte counts.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"175 1","pages":"112-122"},"PeriodicalIF":4.9,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13911","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comparative Analysis of HMC3 and C20 Microglial Cell Lines Reveals Differential Myeloid Characteristics and Responses to Immune Stimuli HMC3和C20小胶质细胞系的对比分析揭示了不同的髓系特征和对免疫刺激的反应。
IF 4.9 3区 医学
Immunology Pub Date : 2025-02-17 DOI: 10.1111/imm.13900
Bavani Gunasegaran, Shivani Krishnamurthy, Sharron S. Chow, Millijoy D. Villanueva, Anna Guller, Seong Beom Ahn, Benjamin Heng
{"title":"Comparative Analysis of HMC3 and C20 Microglial Cell Lines Reveals Differential Myeloid Characteristics and Responses to Immune Stimuli","authors":"Bavani Gunasegaran,&nbsp;Shivani Krishnamurthy,&nbsp;Sharron S. Chow,&nbsp;Millijoy D. Villanueva,&nbsp;Anna Guller,&nbsp;Seong Beom Ahn,&nbsp;Benjamin Heng","doi":"10.1111/imm.13900","DOIUrl":"10.1111/imm.13900","url":null,"abstract":"<p>Microglia are the primary resident immune cells of the central nervous system (CNS) that respond to injury and infections. Being critical to CNS homeostasis, microglia also have been shown to contribute to neurodegenerative diseases and brain cancer. Hence, microglia are regarded as a potential therapeutic target in CNS diseases, resulting in an increased demand for reliable in vitro models. Two human microglia cell lines (HMC3 and C20) are being used in multiple in vitro studies, however, the knowledge of their biological and immunological characteristics remains limited. Our aim was to identify and compare the biological changes in these immortalised immune cells under normal physiological and immunologically challenged conditions. Using high-resolution quantitative mass spectrometry, we have examined in-depth proteomic profiles of non-stimulated and LPS or IFN-γ challenged HMC3 and C20 cells. Our findings reveal that HMC3 cells responded to both treatments through upregulation of immune, metabolic, and antiviral pathways, while C20 cells showed a response associated with mitochondrial and immune activities. Additionally, the secretome analysis demonstrated that both cell lines release IL-6 in response to LPS, while IFN-γ treatment resulted in altered kynurenine pathway activity, highlighting distinct immune and metabolic adaptations.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"175 1","pages":"84-102"},"PeriodicalIF":4.9,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13900","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Lineage Tracking Dissects the Fate of Neonatal iNKT Cells Later in Life 谱系追踪剖析新生iNKT细胞在生命后期的命运。
IF 4.9 3区 医学
Immunology Pub Date : 2025-02-17 DOI: 10.1111/imm.13909
Jun Liu, Biao Yang, Danchen Hu, Ning Yuan, Wenhua Li, Zhao Feng, Yanhong Su, Dan Zhang, Xiaofeng Yang, Baojun Zhang
{"title":"Lineage Tracking Dissects the Fate of Neonatal iNKT Cells Later in Life","authors":"Jun Liu,&nbsp;Biao Yang,&nbsp;Danchen Hu,&nbsp;Ning Yuan,&nbsp;Wenhua Li,&nbsp;Zhao Feng,&nbsp;Yanhong Su,&nbsp;Dan Zhang,&nbsp;Xiaofeng Yang,&nbsp;Baojun Zhang","doi":"10.1111/imm.13909","DOIUrl":"10.1111/imm.13909","url":null,"abstract":"<div>\u0000 \u0000 <p>Invariant natural killer T (iNKT) cells in peripheral tissues are from different waves ranged from foetal, neonatal to adult ages. However, it is unclear how iNKT cells from different ages maintain in the periphery and what are their functionality. We found that in adult mice, neonate tracked-iNKT (NT-iNKT) cells are present in spleen, bone marrow, liver and lung, with a predominantly accumulation in the kidney. The NT-iNKT cells in the kidney are almost iNKT1 cells and express tissue-resident marker CD69. These cells also exhibit higher level of CD122 and possess a stronger proliferative capacity compared to adult tracked-iNKT (AT-iNKT) cells. Furthermore, we found that NT-iNKT cells potentially secrete more IFN-γ than AT-iNKT cells in vitro and in vivo (a-GalCer immunisation). Overall, our study sheds light on the peripheral behaviour and functionality of NT- and AT-iNKT cells, highlighting the potential role of NT-iNKT cells in the kidney during immune response.</p>\u0000 </div>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"175 1","pages":"103-111"},"PeriodicalIF":4.9,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Icariin Induces Chondrocyte Degeneration via Activation of the NF-κB Signalling Pathway and Reduces the Inflammation Factor Expression Induced by Lipopolysaccharide 淫羊藿苷通过激活NF-κB信号通路诱导软骨细胞变性,降低脂多糖诱导的炎症因子表达。
IF 4.9 3区 医学
Immunology Pub Date : 2025-02-13 DOI: 10.1111/imm.13906
Tianjun Zhai, Jie Wang, Yeping Chen, Jianqing Su, Wei Feng
{"title":"Icariin Induces Chondrocyte Degeneration via Activation of the NF-κB Signalling Pathway and Reduces the Inflammation Factor Expression Induced by Lipopolysaccharide","authors":"Tianjun Zhai,&nbsp;Jie Wang,&nbsp;Yeping Chen,&nbsp;Jianqing Su,&nbsp;Wei Feng","doi":"10.1111/imm.13906","DOIUrl":"10.1111/imm.13906","url":null,"abstract":"<div>\u0000 \u0000 <p>To investigate the effect of icariin on chondrocytes by activating the nuclear factor kappa-B (NF-κB) signalling pathway and the mechanism of icariin in inducing chondrocytes degeneration. Chondrocytes were cultured in vitro and treated with icariin at concentrations of 0, 0.01, 0.1, 10 and 20 μm. Cell proliferation was evaluated by cell counting kit-8 (CCK8) method, apoptosis was detected by TUNEL method and the expression of NF-κB was detected by Western blotting (WB) and RT-PCR. The nuclear localization of NF-κB p65 protein was observed by immunofluorescence staining. Lipopolysaccharide (LPS) was used to establish the inflammatory model, and WB and RT-PCR were used to detect the expression levels of tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6). After treatment with icariin, the proliferation ability of chondrocytes was markedly enhanced, and the apoptosis rate (AR) was markedly decreased (<i>p &lt;</i> 0.05). In addition, icariin could inhibit the nuclear translocation of NF-κB p65 protein, promote the gene expression of Collagen II (Col-II) and Aggrecan in chondrocytes, and reduce the expression of NF-κB. Moreover, icariin markedly reduced the expression of IL-6 and TNF-α in LPS-induced inflammation (<i>p &lt;</i> 0.05). Icariin can enhance chondrocyte proliferation, promote phenotypic gene expression by inhibiting the NF-κB signal transduction pathways, thus suppressing the chondrocyte degeneration, and can reduce the inflammation factor expression induced by LPS.</p>\u0000 </div>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"175 1","pages":"76-83"},"PeriodicalIF":4.9,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Maternal Carriage of Prevotella copri Is Associated With Increased Thymus Derived Naïve Regulatory T Cells in Cord Blood 母体携带copri普雷沃氏菌与脐带血中胸腺来源Naïve调节性T细胞增加有关。
IF 4.9 3区 医学
Immunology Pub Date : 2025-02-13 DOI: 10.1111/imm.13904
Yuan Gao, Martin O'Hely, Fiona Collier, Anne-Louise Ponsonby, Mimi L. K. Tang, John Molloy, Peter Vuillermin, the BIS Investigator Group
{"title":"Maternal Carriage of Prevotella copri Is Associated With Increased Thymus Derived Naïve Regulatory T Cells in Cord Blood","authors":"Yuan Gao,&nbsp;Martin O'Hely,&nbsp;Fiona Collier,&nbsp;Anne-Louise Ponsonby,&nbsp;Mimi L. K. Tang,&nbsp;John Molloy,&nbsp;Peter Vuillermin,&nbsp;the BIS Investigator Group","doi":"10.1111/imm.13904","DOIUrl":"10.1111/imm.13904","url":null,"abstract":"","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"174 4","pages":"481-484"},"PeriodicalIF":4.9,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Impact of Pre-Infection COVID-19 Vaccination on the Incidence and Severity of Long COVID: A Retrospective Case–Control Study 感染前接种COVID-19疫苗对长期COVID发病率和严重程度的影响:一项回顾性病例对照研究
IF 4.9 3区 医学
Immunology Pub Date : 2025-02-11 DOI: 10.1111/imm.13908
Elena Barado, Silvia Carlos, Laura Moreno-Galarraga, Fares Amer, Nicolás Escrivá, María Gabriela Torres, Gabriel Reina, Alejandro Fernandez-Montero
{"title":"Impact of Pre-Infection COVID-19 Vaccination on the Incidence and Severity of Long COVID: A Retrospective Case–Control Study","authors":"Elena Barado,&nbsp;Silvia Carlos,&nbsp;Laura Moreno-Galarraga,&nbsp;Fares Amer,&nbsp;Nicolás Escrivá,&nbsp;María Gabriela Torres,&nbsp;Gabriel Reina,&nbsp;Alejandro Fernandez-Montero","doi":"10.1111/imm.13908","DOIUrl":"10.1111/imm.13908","url":null,"abstract":"<div>\u0000 \u0000 <p>Long COVID is an emerging condition with an important impact on the quality of life of affected individuals. This study aims to analyse the association between complete vaccination prior to SARS-CoV-2 infection and the subsequent development of long COVID, including its symptoms and their frequency through a retrospective case–control study. Cases included participants with long COVID, while controls were participants without long COVID but who had a SARS-CoV-2 infection. Data were collected through a self-reported survey. The study demonstrates a significant association between vaccination and a lower incidence of long COVID, adjusted for sex, age, university education, body mass index, physical activity, race, tobacco use, alcohol intake, adherence to Mediterranean diet, previous illness, flu vaccination, health care worker, high-risk COVID worker and sleep hours and sedentarism (OR 0.49, CI 95% 0.28–0.87). Furthermore, there is a statistically significant association between vaccination and reduced symptoms such as anosmia, dysgeusia, myalgia or arthralgia, as well as a lower overall number, adjusted for the aforementioned variables. These findings suggest that the vaccine could be associated not only to a milder course of SARS-CoV-2 infection but also with an improvement in the state of long COVID and its symptoms.</p>\u0000 </div>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"175 1","pages":"67-75"},"PeriodicalIF":4.9,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
X-Ray Crystallography Based Epitope Mapping of Glycoproteins and RNA in Chandipura Vesiculovirus for Vaccine Design 基于x射线晶体学的钱迪普勒囊泡病毒糖蛋白和RNA表位定位及其疫苗设计。
IF 4.9 3区 医学
Immunology Pub Date : 2025-02-04 DOI: 10.1111/imm.13907
Aron Rodrick Lakra
{"title":"X-Ray Crystallography Based Epitope Mapping of Glycoproteins and RNA in Chandipura Vesiculovirus for Vaccine Design","authors":"Aron Rodrick Lakra","doi":"10.1111/imm.13907","DOIUrl":"10.1111/imm.13907","url":null,"abstract":"<div>\u0000 \u0000 <p>This study investigates potential epitopes in the glycoprotein and RNA of Chandipura vesiculovirus (CHPV) using MHC Class I (HLA-A0201) and MHC Class II (DRB1_0101) molecules with 3D structures derived from x-ray crystallography. Computationally derived peptides were mapped and subjected to in silico docking, revealing promising targets for CD8+ cytotoxic and CD4+ helper T cells. Key factors analysed include solvent accessible surface area (SASA), Debye-Waller factor (B-factor), and polar bond interactions. Post-docking, removal of <i>N</i>-acetylglucosamine (NAG) increased peptide stability and reduced B-factors, while SO4 presence had minimal impact. SASA values increased by up to 237.5% with MHC Class I, and RNA docking with MHC Class II displayed mixed SASA changes. Polar bond interactions also increased post-docking, indicating the strong potential of identified CHPV epitopes.</p>\u0000 </div>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"175 1","pages":"52-66"},"PeriodicalIF":4.9,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Novel Polymersome Nanocarrier Promotes Anti-Tumour Immunity by Improved Priming of CD8 + T Cells 一种新的聚合体纳米载体通过改善CD8+ T细胞的启动促进抗肿瘤免疫。
IF 4.9 3区 医学
Immunology Pub Date : 2025-01-28 DOI: 10.1111/imm.13903
Regine J. Dress, William W. Ho, Victor Ho, Jian Hang Lam, Fabien M. Décaillot, Gaurav Sinsinbar, Jenetta Soo, Gowshika Rengasamy, Amit Kumar Khan, Thomas Andrew Cornell, Teck Wan Chia, Shrinivas Venkataraman, Madhavan Nallani, Florent Ginhoux
{"title":"A Novel Polymersome Nanocarrier Promotes Anti-Tumour Immunity by Improved Priming of CD8\u0000 + T Cells","authors":"Regine J. Dress,&nbsp;William W. Ho,&nbsp;Victor Ho,&nbsp;Jian Hang Lam,&nbsp;Fabien M. Décaillot,&nbsp;Gaurav Sinsinbar,&nbsp;Jenetta Soo,&nbsp;Gowshika Rengasamy,&nbsp;Amit Kumar Khan,&nbsp;Thomas Andrew Cornell,&nbsp;Teck Wan Chia,&nbsp;Shrinivas Venkataraman,&nbsp;Madhavan Nallani,&nbsp;Florent Ginhoux","doi":"10.1111/imm.13903","DOIUrl":"10.1111/imm.13903","url":null,"abstract":"<p>Cancer is one of the leading causes of death worldwide. In recent years, immune checkpoint inhibitor therapies, in addition to standard immuno- or chemotherapy and surgical approaches, have massively improved the outcome for cancer patients. However, these therapies have their limitations and improved strategies, including access to reliable cancer vaccines, are needed. Here, we describe the use of self-assembling artificial cell membrane (ACM) polymersomes to deliver tumour-specific peptides to trigger sustainable and efficient anti-tumour immune responses. We found that ACM polymersomes were highly efficient in targeting and activating mononuclear phagocytes (MNP) including dendritic cells (DC), while providing long-term reservoirs of antigens for continued immune cell priming. Subcutaneous injection of ACM-encapsulated tumour-antigen-peptides into tumour-bearing mice resulted in improved priming of CD8<sup>+</sup> T cells and increased generation of tumour-antigen-peptide specific CD8<sup>+</sup> effector T cells. Prophylactic and therapeutic immunisation with ACM-encapsulated peptides resulted in changes to the MNP composition in the tumour microenvironment, tumour regression and improved survival of immunised mice. Combining anti-PD-1 immune checkpoint inhibitor therapy with ACM polymersome peptide delivery further boosted anti-tumour immunity. Our results show that ACM polymersome nanocarriers efficiently instruct anti-tumour immune responses offering a promising new approach for vaccination and cancer immunotherapy.</p><p>\u0000 <b>Trial Registration:</b> NCT05385991</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"175 1","pages":"21-35"},"PeriodicalIF":4.9,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13903","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Epstein–Barr Virus-Induced 3 Attributes to TLR7-Mediated Splenomegaly eb病毒诱导的tlr7介导的脾肿大的3个特性。
IF 4.9 3区 医学
Immunology Pub Date : 2025-01-28 DOI: 10.1111/imm.13905
Masanori Iseki, Yuma Sakamoto, Daiki Takezaki, Yoshihiro Matsuda, Mariko Inoue, Shin Morizane, Tomoyuki Mukai
{"title":"Epstein–Barr Virus-Induced 3 Attributes to TLR7-Mediated Splenomegaly","authors":"Masanori Iseki,&nbsp;Yuma Sakamoto,&nbsp;Daiki Takezaki,&nbsp;Yoshihiro Matsuda,&nbsp;Mariko Inoue,&nbsp;Shin Morizane,&nbsp;Tomoyuki Mukai","doi":"10.1111/imm.13905","DOIUrl":"10.1111/imm.13905","url":null,"abstract":"<div>\u0000 \u0000 <p>Epstein–Barr virus-induced 3 (EBI3) functions as a component of the heterodimer cytokine IL-27, which regulates innate and acquired immune responses. The expression of EBI3 gene is induced by Toll-like receptors (TLRs). Repeated treatment with imiquimod (IMQ), a TLR7 agonist, induces splenomegaly and cytopaenia due to increased splenic function. Although immune cell activation is speculated to play a role in chronic infection-mediated splenomegaly, the detailed mechanisms remain unknown. This study shows that IMQ treatment induces marked splenomegaly and severe bicytopaenia (anaemia and thrombocytopaenia) in wild-type mice. In IMQ-treated mice, myeloid cell populations in the spleen increased, and extramedullary haematopoiesis was observed. RNA-seq analysis revealed the upregulation of type I interferon (IFN)-related genes in the spleens of IMQ-treated mice. IMQ-induced pathological changes were partially mitigated by EBI3 deficiency. To investigate the mechanism of the improved phenotypes in the <i>Ebi3</i> KO mice, we examined the involvement of IL-27, a heterodimer of EBI3 and IL-27p28. The expression of <i>Il27a</i>, which encodes IL-27p28, was increased in the spleen and peripheral blood by IMQ treatment. Furthermore, IL-27 stimulation upregulated type I IFN-related genes in bone marrow-derived macrophage cultures without type I IFN. These findings suggest that EBI3 deficiency mitigated IMQ-mediated pathological changes, presumably via a lack of IL-27 formation. Our study thus provides insights into the molecular mechanisms underlying chronic infection-mediated splenomegaly.</p>\u0000 </div>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"175 1","pages":"36-51"},"PeriodicalIF":4.9,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Renal and Peripheral Blood Transcriptome Signatures That Predict Treatment Response in Proliferative Lupus Nephritis—A Prospective Study 预测增殖性狼疮性肾炎治疗反应的肾脏和外周血转录组特征-一项前瞻性研究。
IF 4.9 3区 医学
Immunology Pub Date : 2025-01-28 DOI: 10.1111/imm.13891
Sree Nethra Bulusu, Anitha Nagaraj Bavikatte, Sanket Shah, Sneha Surya Narayana Murthy, Vallayyachari Kommoju, Christina Mary Mariaselvam, Chengappa Kavadichanda, Shruthi Sridhar Vembar, Molly Mary Thabah, Vir Singh Negi
{"title":"Renal and Peripheral Blood Transcriptome Signatures That Predict Treatment Response in Proliferative Lupus Nephritis—A Prospective Study","authors":"Sree Nethra Bulusu,&nbsp;Anitha Nagaraj Bavikatte,&nbsp;Sanket Shah,&nbsp;Sneha Surya Narayana Murthy,&nbsp;Vallayyachari Kommoju,&nbsp;Christina Mary Mariaselvam,&nbsp;Chengappa Kavadichanda,&nbsp;Shruthi Sridhar Vembar,&nbsp;Molly Mary Thabah,&nbsp;Vir Singh Negi","doi":"10.1111/imm.13891","DOIUrl":"10.1111/imm.13891","url":null,"abstract":"<div>\u0000 \u0000 <p>Mechanisms contributing to non-response to treatment in lupus nephritis (LN) are unclear. We characterised the transcriptome of paired peripheral blood mononuclear cells (PBMCs) and renal tissues in LN before and after cyclophosphamide (CYC) treatment and identified markers that predicted treatment response. Total RNA isolated from paired PBMCs (<i>n</i> = 32) and renal tissues (<i>n</i> = 25) of 16 proliferative LN before CYC treatment, 6 months post-treatment, and during renal flare, was sequenced on Illumina Novaseq-6000 platform. Post-treatment, eight patients were clinical responders (CR), of whom four flared (FL), and eight were non-responders (NR). Comparative transcriptomic analyses before and after treatment within CR, NR, and FL groups was performed using DESeq2. Weighted gene co-expression network analysis (WGCNA) and ROC analysis was performed to identify and validate hub genes predictive of treatment response. Based on this, we observed that pathways such as degradation of cell cycle proteins, expression of G0 and G1 phase proteins, and apoptosis, were upregulated in CR PBMCs post-treatment, while IFN-γ signalling and ECM organisation were downregulated. In NR PBMCs, ECM molecules, neddylation and BCR signalling were upregulated post-CYC treatment, while in NR renal tissue, TLR, IFN and NF-κB signalling pathways were upregulated. In FL PBMCs, neutrophil degranulation and ROS and RNS production in phagocytes were downregulated following treatment, whereas, in the corresponding renal tissue, cell-ECM interactions and <i>ISG15</i> antiviral mechanism were downregulated. After WGCNA and subsequent ROC analysis, <i>TENM2, NLGN1</i> and <i>AP005230.1</i> from PBMCs each predicted NR (AUC-0.91; <i>p</i> = 0.03), while combined model improved prediction (AUC-0.94; <i>p</i> = 0.02). <i>AP005230.1</i> from renal tissue also predicted non-response (AUC-0.94; <i>p</i> = 0.01) and <i>AC092436.3</i> from PBMCs predicted renal flare (AUC-0.81; <i>p</i> = 0.04). Our study identified significant DEGs/pathways specific to different treatment outcomes and hub genes that predicted non-response and renal flare.</p>\u0000 </div>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"174 4","pages":"470-480"},"PeriodicalIF":4.9,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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