European Journal of Immunology最新文献

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Type I Interferon Drives a Cellular State Inert to TCR-Stimulation and Could Impede Effective T-Cell Differentiation in Cancer. I 型干扰素驱动一种对 TCR 刺激惰性的细胞状态,并可能阻碍癌症中 T 细胞的有效分化。
IF 4.5 3区 医学
European Journal of Immunology Pub Date : 2024-11-12 DOI: 10.1002/eji.202451371
Dillon Corvino, Martin Batstone, Brett G M Hughes, Tim Kempchen, Susanna S Ng, Nazhifah Salim, Franziska Schneppenheim, Denise Rommel, Ananthi Kumar, Sally Pearson, Jason Madore, Lambross T Koufariotis, Lisa Maria Steinheuer, Dilan Pathirana, Kevin Thurley, Michael Hölzel, Nicholas Borcherding, Matthias Braun, Tobias Bald
{"title":"Type I Interferon Drives a Cellular State Inert to TCR-Stimulation and Could Impede Effective T-Cell Differentiation in Cancer.","authors":"Dillon Corvino, Martin Batstone, Brett G M Hughes, Tim Kempchen, Susanna S Ng, Nazhifah Salim, Franziska Schneppenheim, Denise Rommel, Ananthi Kumar, Sally Pearson, Jason Madore, Lambross T Koufariotis, Lisa Maria Steinheuer, Dilan Pathirana, Kevin Thurley, Michael Hölzel, Nicholas Borcherding, Matthias Braun, Tobias Bald","doi":"10.1002/eji.202451371","DOIUrl":"https://doi.org/10.1002/eji.202451371","url":null,"abstract":"<p><strong>Background: </strong>Head and neck squamous cell carcinoma (HNSCC) is linked to human papillomavirus (HPV) infection. HPV-positive and HPV-negative HNSCC exhibit distinct molecular and clinical characteristics. Although checkpoint inhibitors have shown efficiency in recurrent/metastatic HNSCC, response variability persists regardless of HPV status. This study aimed to explore the CD8<sup>+</sup> T-cell landscape in HPV-negative HNSCC.</p><p><strong>Methods: </strong>We performed simultaneous single-cell RNA and TCR sequencing of CD8<sup>+</sup> tumor-infiltrating lymphocytes (TILs) from treatment-naïve HPV-negative HNSCC patients. Additionally, cells were stimulated ex vivo, which allowed for the tracking of clonal transcriptomic responses.</p><p><strong>Results: </strong>Our analysis identified a subset of CD8<sup>+</sup> TILs highly enriched for interferon-stimulated genes (ISG). TCR analysis revealed ISG cells are clonally related to a population of granzyme K (GZMK)-expressing cells. However, unlike GZMK cells, which exhibited rapid effector-like phenotypes following stimulation, ISG cells were transcriptionally inert. Additionally, ISG cells showed specific enrichment within tumor and were found across multiple tumor entities.</p><p><strong>Conclusions: </strong>ISG-enriched CD8<sup>+</sup> TILs are a consistent feature of various tumor entities. These cells are poorly understood but possess characteristics that may impact antitumor immunity. Understanding the unique properties and functionality of ISG cells could offer innovative treatment approaches to improve patient outcomes in HPV-negative HNSCC and other cancer types.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e202451371"},"PeriodicalIF":4.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613195","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
B Cells With Complementary B Cell Receptors Can Kill Each Other. 具有互补 B 细胞受体的 B 细胞可以互相杀伤
IF 4.5 3区 医学
European Journal of Immunology Pub Date : 2024-11-09 DOI: 10.1002/eji.202350890
Ramakrishna Prabhu Gopalakrishnan, Marius Sigurdsson Østrøm, Frode Miltzow Skjeldal, Oddmund Bakke, Bjarne Bogen, Peter Csaba Huszthy
{"title":"B Cells With Complementary B Cell Receptors Can Kill Each Other.","authors":"Ramakrishna Prabhu Gopalakrishnan, Marius Sigurdsson Østrøm, Frode Miltzow Skjeldal, Oddmund Bakke, Bjarne Bogen, Peter Csaba Huszthy","doi":"10.1002/eji.202350890","DOIUrl":"https://doi.org/10.1002/eji.202350890","url":null,"abstract":"<p><p>B cells differentiate from hematopoietic stem cells in the bone marrow (BM) and migrate as transitional cells to the spleen where final maturation takes place. Due to the enormous diversity in variable (V) regions of B cell receptors for antigen (BCR), B cells with complementary BCRs are likely to be generated. These could encounter each other in the BM or in secondary lymphoid organs. The outcome of such an event is unknown. To study this issue, we used two strains of gene-modified mice whose B cells display complementary BCRs. B cells of one strain express an idiotype<sup>+</sup> (Id<sup>+</sup>) BCR while B cells of the other strain display an anti-idiotypic (αId) BCR. In vitro, B cells with complementary BCRs killed each other in a mechanism that required physical binding between BCR V-regions. In contrast, killing was unilateral in vivo: αId B cells with a follicular (FO) B cell phenotype were expanded, while Id<sup>+</sup> B cells with a marginal zone (MZ) phenotype became deleted. The results show that B cells with complementary BCRs can recognize and regulate each other in vivo. This mechanism should be taken into account in theories for idiotypic regulation of the immune system.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e202350890"},"PeriodicalIF":4.5,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613193","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
Characterization of the Molecular Signature of Human Monocytes in Aging and Myelodysplastic Neoplasms. 人类单核细胞在衰老和骨髓增生异常肿瘤中的分子特征。
IF 4.5 3区 医学
European Journal of Immunology Pub Date : 2024-11-08 DOI: 10.1002/eji.202451387
Christina Maria Rimpa, Maria Grigoriou, Athanasios Tasis, Nikolaos Paschalidis, Anastasia Filia, Giannis Vatsellas, Panagiotis Papazoglou, Antonios Chatzigeorgiou, Chrysa Kymparidou, Menelaos Papoutselis, Christina Misidou, Theodoros Spyropoulos, Despoina Dimitriou, Haralampos Hatzikirou, Konstantinos Liapis, Eleftheria Lamprianidou, Ioannis Kotsianidis, Ioannis Mitroulis
{"title":"Characterization of the Molecular Signature of Human Monocytes in Aging and Myelodysplastic Neoplasms.","authors":"Christina Maria Rimpa, Maria Grigoriou, Athanasios Tasis, Nikolaos Paschalidis, Anastasia Filia, Giannis Vatsellas, Panagiotis Papazoglou, Antonios Chatzigeorgiou, Chrysa Kymparidou, Menelaos Papoutselis, Christina Misidou, Theodoros Spyropoulos, Despoina Dimitriou, Haralampos Hatzikirou, Konstantinos Liapis, Eleftheria Lamprianidou, Ioannis Kotsianidis, Ioannis Mitroulis","doi":"10.1002/eji.202451387","DOIUrl":"https://doi.org/10.1002/eji.202451387","url":null,"abstract":"<p><p>• Aging leads to chronic inflammation and immune dysfunction, heightening the risk of myeloid malignancies like MDS and CMML. • Both aging and MDS show alterations in monocyte subtypes and function. Aging boosts inflammatory genes upregulation, whereas MDS favors antigen presentation, reflecting distinct immune and disease-specific adaptations. • MDS shows reduced inflammatory activity in CD14<sup>+</sup> cells, whereas CMML exhibits heightened inflammation, highlighting distinct disease mechanisms.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e202451387"},"PeriodicalIF":4.5,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602527","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
Rise of a CD27− IgD− CD11c+ B cells population in kidney recipients achieving long-term graft stability under immunosuppression 在免疫抑制条件下实现长期移植稳定性的肾脏受者体内 CD27- IgD- CD11c+ B 细胞群的崛起。
IF 4.5 3区 医学
European Journal of Immunology Pub Date : 2024-11-07 DOI: 10.1002/eji.202451143
François Brinas, Nicolas Sailliet, Gaëlle Tilly, Laurence Delbos, Clarisse Kerleau, Magali Giral, Nicolas Degauque, Sophie Brouard, Richard Danger
{"title":"Rise of a CD27− IgD− CD11c+ B cells population in kidney recipients achieving long-term graft stability under immunosuppression","authors":"François Brinas,&nbsp;Nicolas Sailliet,&nbsp;Gaëlle Tilly,&nbsp;Laurence Delbos,&nbsp;Clarisse Kerleau,&nbsp;Magali Giral,&nbsp;Nicolas Degauque,&nbsp;Sophie Brouard,&nbsp;Richard Danger","doi":"10.1002/eji.202451143","DOIUrl":"10.1002/eji.202451143","url":null,"abstract":"<p>The use of immunosuppressive treatment is required to prevent rejection events, even a long time after kidney transplantation despite rare recipients achieving long-term graft stability without the need for immunosuppressive treatment, called operationally tolerant patients (TOLs). We comprehensively investigate the immune system of long-term IS recipients (LTTs) and TOLs to highlight their shared and unique immune features. Blood immune cell phenotyping was performed by spectral cytometry. Samples from 34 individuals were analyzed, including 6 LTTs, 8 TOLs, 10 stable patients at 1 year posttransplantation (STAs), and 10 healthy volunteers. B cells differed between LTTs and TOLs with a decreased total B-cell frequency and the acquisition of a memory phenotype in LTTs whereas a naive phenotype is maintained in TOLs. The frequencies of IgD<sup>−</sup>CD27<sup>−</sup> B cells and CD11c<sup>+</sup> memory B cells are increased in LTTs, with an exhausted phenotype, evoked by a significant decrease in CD25 expression. These CD11c<sup>+</sup> B cells display an exhausted phenotype similar to those found in several chronic immune diseases in which they have been shown to participate in their pathophysiology, suggesting active chronic inflammation in LTTs. Altogether, these data indicate that precautions should be taken to minimize IS use.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"54 12","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602531","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
Issue Information: Eur. J. Immunol. 11'24 发行信息:Eur.J. Immunol.11'24
IF 4.5 3区 医学
European Journal of Immunology Pub Date : 2024-11-07 DOI: 10.1002/eji.202470112
{"title":"Issue Information: Eur. J. Immunol. 11'24","authors":"","doi":"10.1002/eji.202470112","DOIUrl":"https://doi.org/10.1002/eji.202470112","url":null,"abstract":"","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"54 11","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202470112","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142640552","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
Neutrophil Extracellular Traps Participate in the Pathogenesis of Lupus Through S100A10-Mediated Regulatory T-Cell Differentiation and Functional Abnormalities. 中性粒细胞胞外陷阱通过 S100A10 介导的调节性 T 细胞分化和功能异常参与红斑狼疮的发病机制
IF 4.5 3区 医学
European Journal of Immunology Pub Date : 2024-11-07 DOI: 10.1002/eji.202451298
Hua Guo, Qian Liang, Zhonghui Xue, Junling Yang, Pengyu Chen, Juan Ji, Jing Li, Genkai Guo, Haixia Cao, Xiaoqi Sha, Rui Zhao, Chen Dong, Zhifeng Gu
{"title":"Neutrophil Extracellular Traps Participate in the Pathogenesis of Lupus Through S100A10-Mediated Regulatory T-Cell Differentiation and Functional Abnormalities.","authors":"Hua Guo, Qian Liang, Zhonghui Xue, Junling Yang, Pengyu Chen, Juan Ji, Jing Li, Genkai Guo, Haixia Cao, Xiaoqi Sha, Rui Zhao, Chen Dong, Zhifeng Gu","doi":"10.1002/eji.202451298","DOIUrl":"https://doi.org/10.1002/eji.202451298","url":null,"abstract":"<p><p>In systemic lupus erythematosus (SLE), neutrophil dysregulation and neutrophil extracellular traps (NETs) formation contribute to disease pathogenesis, potentially worsening the autoimmune response. Although research indicates NETs' involvement in various autoimmune conditions, their relationship with regulatory T cells (Tregs) in SLE remains elusive. In this study, in vivo experiments were involved in administering NET injections to C57BL/6 and MRL/Ipr mice. In vitro, a co-culture system facilitated interaction between Tregs and NETs. Proteomic analysis elucidated NET composition, while RNA sequencing delineated their impact on Treg differentiation. We demonstrated that increased NET levels correlate inversely with Treg abundance in SLE patients, influencing both their proportion and functionality. NET administration reduced Treg levels and induced lupus-like symptoms in C57BL/6 mice, exacerbating symptoms in MRL/Ipr mice. DNase I treatment mitigated NET effects, restoring Treg levels and alleviating symptoms. RNA sequencing revealed altered gene expression in naïve CD4<sup>+</sup> T cells exposed to NETs. Additionally, proteomic analysis showed S100A10 protein changes between SLE patients and healthy controls, hindering Treg differentiation. NETs influence TLR-4 of naïve CD4<sup>+</sup> T cells via S100A10, thereby modulating Treg proportion and functionality. These findings highlight the critical role of NETs in Treg differentiation in SLE, suggesting that targeting NETs may provide a novel therapeutic approach.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e202451298"},"PeriodicalIF":4.5,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602528","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
Cover Story: Eur. J. Immunol. 11'24 封面故事Eur.J. Immunol.11'24
IF 4.5 3区 医学
European Journal of Immunology Pub Date : 2024-11-07 DOI: 10.1002/eji.202470111
{"title":"Cover Story: Eur. J. Immunol. 11'24","authors":"","doi":"10.1002/eji.202470111","DOIUrl":"https://doi.org/10.1002/eji.202470111","url":null,"abstract":"<p>Our cover features images related to flow cytometry techniques widely used for analysis of function and phenotypes of major human and murine immune cell subsets, superimposed on a multidimensional immune cell population scatter plot. These images are taken from the third edition of EJI's Flow Cytometry Guidelines by Cossarizza et al., a comprehensive resource prepared by flow cytometry and immunology research experts from around the world.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"54 11","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202470111","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142641562","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
Impressum 印象深刻。
IF 4.5 3区 医学
European Journal of Immunology Pub Date : 2024-11-07 DOI: 10.1002/eji.202470113
{"title":"Impressum","authors":"","doi":"10.1002/eji.202470113","DOIUrl":"10.1002/eji.202470113","url":null,"abstract":"","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"54 11","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589806","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
The VEGF-Mediated Cytoprotective Ability of MIF-Licensed Mesenchymal Stromal Cells in House Dust Mite-Induced Epithelial Damage. MIF 许可的间充质基质细胞在室尘螨诱导的上皮损伤中的血管内皮生长因子介导的细胞保护能力
IF 4.5 3区 医学
European Journal of Immunology Pub Date : 2024-11-06 DOI: 10.1002/eji.202451205
Hazel Dunbar, Ian J Hawthorne, Courteney Tunstead, Molly Dunlop, Evelina Volkova, Daniel J Weiss, Claudia C Dos Santos, Michelle E Armstrong, Seamas C Donnelly, Karen English
{"title":"The VEGF-Mediated Cytoprotective Ability of MIF-Licensed Mesenchymal Stromal Cells in House Dust Mite-Induced Epithelial Damage.","authors":"Hazel Dunbar, Ian J Hawthorne, Courteney Tunstead, Molly Dunlop, Evelina Volkova, Daniel J Weiss, Claudia C Dos Santos, Michelle E Armstrong, Seamas C Donnelly, Karen English","doi":"10.1002/eji.202451205","DOIUrl":"https://doi.org/10.1002/eji.202451205","url":null,"abstract":"<p><p>Enhancing mesenchymal stromal cell (MSC) therapeutic efficacy through licensing with proinflammatory cytokines is now well established. We have previously shown that macrophage migration inhibitory factor (MIF)-licensed MSCs exerted significantly enhanced therapeutic efficacy in reducing inflammation in house dust mite (HDM)-driven allergic asthma. Soluble mediators released into the MSC secretome boast cytoprotective properties equal to those associated with the cell itself. In asthma, epithelial barrier damage caused by the inhalation of allergens like HDM drives goblet cell hyperplasia. Vascular endothelial growth factor (VEGF) plays a pivotal role in the repair and maintenance of airway epithelial integrity. Human bone marrow-derived MSCs expressed the MIF receptors CD74, CXCR2, and CXCR4. Endogenous MIF from high MIF expressing CATT<sub>7</sub> bone marrow-derived macrophages increased MSC production of VEGF through the MIF CXCR4 chemokine receptor, where preincubation with CXCR4 inhibitor mitigated this effect. CATT<sub>7</sub>-MIF licensed MSC conditioned media containing increased levels of VEGF significantly enhanced bronchial epithelial wound healing via migration and proliferation in vitro. Blocking VEGFR2 or the use of mitomycin C abrogated this effect. Furthermore, CATT<sub>7</sub>-MIF MSC CM significantly decreased goblet cell hyperplasia after the HDM challenge in vivo. This was confirmed to be VEGF-dependent, as the use of anti-human VEGF neutralising antibody abrogated this effect. Overall, this study highlights that MIF-licenced MSCs show enhanced production of VEGF, which has the capacity to repair the lung epithelium.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e202451205"},"PeriodicalIF":4.5,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581412","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
Alveolar epithelial cells shape lipopolysaccharide-induced inflammatory responses and reprogramming of alveolar macrophages. 肺泡上皮细胞塑造脂多糖诱导的炎症反应和肺泡巨噬细胞的重编程。
IF 4.5 3区 医学
European Journal of Immunology Pub Date : 2024-11-05 DOI: 10.1002/eji.202350378
Wei Jiang, Yeying Chen, Cheng-Yun Yu, Benkun Zou, Yimeng Lu, Qian Yang, Zihui Tang, Weiying Mao, Jing Li, Han Han, Lingyun Shao, Jiashun Zeng, Yiwei Chu, Jianguo Tang, Mingfang Lu
{"title":"Alveolar epithelial cells shape lipopolysaccharide-induced inflammatory responses and reprogramming of alveolar macrophages.","authors":"Wei Jiang, Yeying Chen, Cheng-Yun Yu, Benkun Zou, Yimeng Lu, Qian Yang, Zihui Tang, Weiying Mao, Jing Li, Han Han, Lingyun Shao, Jiashun Zeng, Yiwei Chu, Jianguo Tang, Mingfang Lu","doi":"10.1002/eji.202350378","DOIUrl":"https://doi.org/10.1002/eji.202350378","url":null,"abstract":"<p><p>Alveolar macrophages (AMs) are sentinels in the airways, where they sense and respond to invading microbes and other stimuli. Unlike macrophages in other locations, AMs can remain responsive to Gram-negative lipopolysaccharides (LPS) after they have responded to LPS in vivo (they do not develop \"endotoxin tolerance\"), suggesting that the alveolar microenvironment may influence their responses. Although alveolar epithelial cells (AECs) normally limit AMs' innate responses, preventing inflammation induced by harmless antigens in the lung, how AECs influence the innate responses of AMs to infectious agents has been uncertain. Here we report that (1) after exposure to aspirated (intranasal instillation) LPS, AMs increase their responses to TLR agonists and elevate their phagocytic and bactericidal activities in mice; (2) Aspirated LPS pre-exposure increases host resistance to pulmonary infection caused by Gram-negative bacteria and the protection effect lasts for at least 35 days; (3) LPS stimulation of AECs both increases AMs' innate immune responses and prevents AMs from developing tolerance in vitro; (4) Upon LPS stimulation, AMs secreted TNF-α induces AECs to release GM-CSF, which potentiates AMs' response. These experiments have revealed a previously unappreciated role that AECs may play in boosting the innate responses of AMs and promoting resistance to pulmonary infections.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e2350378"},"PeriodicalIF":4.5,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581373","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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