Journal of Innate Immunity最新文献_第10页

Mannan-Binding Lectin Reduces Epithelial-Mesenchymal Transition in Pulmonary Fibrosis via Inactivating the Store-Operated Calcium Entry Machinery. 甘露聚糖结合凝集素通过抑制储存操作的钙进入机制减少肺纤维化的上皮-间质转化。

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2023-01-01 Epub Date: 2022-06-07 DOI: 10.1159/000524693

Yunzhi Liu, Xianghuan Xie, Ping Wang, Jialiang Luo, Yu Chen, Qishan Xu, Jia Zhou, Xiao Lu, Jianbo Zhao, Zhengliang Chen, Daming Zuo

{"title":"Mannan-Binding Lectin Reduces Epithelial-Mesenchymal Transition in Pulmonary Fibrosis via Inactivating the Store-Operated Calcium Entry Machinery.","authors":"Yunzhi Liu, Xianghuan Xie, Ping Wang, Jialiang Luo, Yu Chen, Qishan Xu, Jia Zhou, Xiao Lu, Jianbo Zhao, Zhengliang Chen, Daming Zuo","doi":"10.1159/000524693","DOIUrl":"10.1159/000524693","url":null,"abstract":"Idiopathic pulmonary fibrosis (IPF) is a type of idiopathic interstitial pneumonia with a poor clinical prognosis. Increasing evidence has demonstrated that epithelial-mesenchymal transition (EMT) contributes to the production of pathogenic myofibroblasts and plays a pivotal role in the development of pulmonary fibrosis. Mannan-binding lectin (MBL) is a soluble calcium-dependent complement molecule. Several studies have reported associations between serum MBL levels and lung diseases; however, the effect of MBL on IPF remains unknown. The present study observed aggravated pulmonary fibrosis in bleomycin-treated MBL-/- mice compared with their wild-type counterparts. Lung tissues from bleomycin-treated MBL-/- mice displayed a more severe EMT phenotype. In vitro studies determined that MBL inhibited the EMT process through attenuating store-operated calcium entry (SOCE) signaling. It was further demonstrated that MBL promoted the ubiquitination of Orai1, an essential component of SOCE, via pyruvate dehydrogenase kinase 1 (PDK1)-serum glucocorticoid-regulated kinase 1 signaling. PDK1 inhibition abolished the MBL-mediated regulation of SOCE activity and the EMT process. Notably, biochemical analysis showed that MBL interacted with PDK1 and contributed to PDK1 ubiquitination. In summary, the present findings suggested that MBL limited the EMT phenotype in human alveolar epithelial cells through regulation of SOCE, and MBL could be recognized as a potential therapeutic target for IPF.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10643902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46587861","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: 2

Human Monocytes Exposed to SARS-CoV-2 Display Features of Innate Immune Memory Producing High Levels of CXCL10 upon Restimulation. 暴露于SARS-CoV-2的人单核细胞表现出先天免疫记忆的特征，在再刺激时产生高水平的CXCL10。

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2023-01-01 Epub Date: 2023-11-21 DOI: 10.1159/000535120

Jelena Cvetkovic, Ronald H J Jacobi, Alberto Miranda-Bedate, Nhung Pham, Martina Kutmon, James Groot, Martijn D B van de Garde, Elena Pinelli

{"title":"Human Monocytes Exposed to SARS-CoV-2 Display Features of Innate Immune Memory Producing High Levels of CXCL10 upon Restimulation.","authors":"Jelena Cvetkovic, Ronald H J Jacobi, Alberto Miranda-Bedate, Nhung Pham, Martina Kutmon, James Groot, Martijn D B van de Garde, Elena Pinelli","doi":"10.1159/000535120","DOIUrl":"10.1159/000535120","url":null,"abstract":"Introduction: A role for innate immune memory in protection during COVID-19 infection or vaccination has been recently reported. However, no study so far has shown whether the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can train innate immune cells. The aim of this study was to investigate whether this virus can induce trained immunity in human monocytes.Methods: Monocytes were exposed to inactivated SARS-CoV-2 (iSARS-CoV-2) for 24 h, followed by a resting period in the medium only and a secondary stimulation on day 6 after which the cytokine/chemokine and transcriptomic profiles were determined.Results: Compared to untrained cells, the iSARS-CoV-2-trained monocytes secreted significantly higher levels of IL-6, TNF-α, CXCL10, CXCL9, and CXCL11 upon restimulation. Transcriptome analysis of iSARS-CoV-2-trained monocytes revealed increased expression of several inflammatory genes. As epigenetic and metabolic modifications are hallmarks of trained immunity, we analyzed the expression of genes related to these processes. Findings indicate that indeed SARS-CoV-2-trained monocytes show changes in the expression of genes involved in metabolic pathways including the tricarboxylic acid cycle, amino acid metabolism, and the expression of several epigenetic regulator genes. Using epigenetic inhibitors that block histone methyl and acetyltransferases, we observed that the capacity of monocytes to be trained by iSARS-CoV-2 was abolished.Conclusion: Overall, our findings indicate that iSARS-CoV-2 can induce properties associated with trained immunity in human monocytes. These results contribute to the knowledge required for improving vaccination strategies to prevent infectious diseases.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10718582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138291091","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

Advanced Glycation End Products-Induced Activation of Keratinocytes: A Mechanism Underlying Cutaneous Immune Response in Psoriasis. 晚期糖基化终产物诱导角化细胞活化:银屑病皮肤免疫反应的机制。

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2023-01-01 Epub Date: 2023-11-21 DOI: 10.1159/000534639

Pan Kang, Jianru Chen, Shiyu Wang, Shaolong Zhang, Shuli Li, Sen Guo, Pu Song, Ling Liu, Gang Wang, Tianwen Gao, Weigang Zhang, Chunying Li

{"title":"Advanced Glycation End Products-Induced Activation of Keratinocytes: A Mechanism Underlying Cutaneous Immune Response in Psoriasis.","authors":"Pan Kang, Jianru Chen, Shiyu Wang, Shaolong Zhang, Shuli Li, Sen Guo, Pu Song, Ling Liu, Gang Wang, Tianwen Gao, Weigang Zhang, Chunying Li","doi":"10.1159/000534639","DOIUrl":"10.1159/000534639","url":null,"abstract":"Psoriasis is a common inflammatory skin disease, in which epidermal keratinocytes play a vital role in its pathogenesis by acting both as the responder and as the accelerator to the cutaneous psoriatic immune response. Advanced glycation end products (AGEs) are a class of proinflammatory metabolites that are commonly accumulating in cardiometabolic disorders. Recent studies have also observed the increased level of AGEs in the serum and skin of psoriasis patients, but the role of AGEs in psoriatic inflammation has not been well investigated. In the present study, we initially detected abnormal accumulation of AGEs in epidermal keratinocytes of psoriatic lesions collected from psoriasis patients. Furthermore, AGEs promoted the proliferation of keratinocytes via upregulated Keratin 17 (K17)-mediated p27KIP1 inhibition followed by accelerated cell cycle progression. More importantly, AGEs facilitated the production of interleukin-36 alpha (IL-36α) in keratinocytes, which could enhance T helper 17 (Th17) immune response. In addition, the induction of both K17 and IL-36α by AGEs in keratinocytes was dependent on the activation of signal transducer and activator of transcription 1/3 (STAT1/3) signaling pathways. At last, the effects of AGEs on keratinocytes were mediated by the receptor for AGEs (RAGE). Taken together, these findings support that AGEs potentiate the innate immune function of keratinocytes, which contributes to the formation of psoriatic inflammation. Our study implicates AGEs as a potential pathogenic link between psoriasis and cardiometabolic comorbidities.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10715758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138291090","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

Impact of Changes in Human Airway Epithelial Cellular Composition and Differentiation on SARS-CoV-2 Infection Biology. 人类气道上皮细胞组成和分化的变化对 SARS-CoV-2 感染生物学的影响

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2023-01-01 Epub Date: 2023-03-25 DOI: 10.1159/000530374

Melissa Thaler, Ying Wang, Anne M van der Does, Alen Faiz, Dennis K Ninaber, Natacha S Ogando, Hendrik Beckert, Christian Taube, Clarisse Salgado-Benvindo, Eric J Snijder, Peter J Bredenbeek, Pieter S Hiemstra, Martijn J van Hemert

{"title":"Impact of Changes in Human Airway Epithelial Cellular Composition and Differentiation on SARS-CoV-2 Infection Biology.","authors":"Melissa Thaler, Ying Wang, Anne M van der Does, Alen Faiz, Dennis K Ninaber, Natacha S Ogando, Hendrik Beckert, Christian Taube, Clarisse Salgado-Benvindo, Eric J Snijder, Peter J Bredenbeek, Pieter S Hiemstra, Martijn J van Hemert","doi":"10.1159/000530374","DOIUrl":"10.1159/000530374","url":null,"abstract":"The consequences of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can range from asymptomatic to fatal disease. Variations in epithelial susceptibility to SARS-CoV-2 infection depend on the anatomical location from the proximal to distal respiratory tract. However, the cellular biology underlying these variations is not completely understood. Thus, air-liquid interface cultures of well-differentiated primary human tracheal and bronchial epithelial cells were employed to study the impact of epithelial cellular composition and differentiation on SARS-CoV-2 infection by transcriptional (RNA sequencing) and immunofluorescent analyses. Changes of cellular composition were investigated by varying time of differentiation or by using specific compounds. We found that SARS-CoV-2 primarily infected not only ciliated cells but also goblet cells and transient secretory cells. Viral replication was impacted by differences in cellular composition, which depended on culturing time and anatomical origin. A higher percentage of ciliated cells correlated with a higher viral load. However, DAPT treatment, which increased the number of ciliated cells and reduced goblet cells, decreased viral load, indicating the contribution of goblet cells to infection. Cell entry factors, especially cathepsin L and transmembrane protease serine 2, were also affected by differentiation time. In conclusion, our study demonstrates that viral replication is affected by changes in cellular composition, especially in cells related to the mucociliary system. This could explain in part the variable susceptibility to SARS-CoV-2 infection between individuals and between anatomical locations in the respiratory tract.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/48/f5/jin-2023-0015-0001-530374.PMC10315690.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9774994","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

TLR7 Activation in M-CSF-Dependent Monocyte-Derived Human Macrophages Potentiates Inflammatory Responses and Prompts Neutrophil Recruitment. M-CSF 依赖性单核细胞衍生的人类巨噬细胞中的 TLR7 激活可增强炎症反应并促进中性粒细胞的招募。

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2023-01-01 Epub Date: 2023-04-11 DOI: 10.1159/000530249

Miriam Simón-Fuentes, Cristina Herrero, Lucia Acero-Riaguas, Concha Nieto, Fatima Lasala, Nuria Labiod, Joanna Luczkowiak, Bárbara Alonso, Rafael Delgado, Maria Colmenares, Ángel L Corbí, Ángeles Domínguez-Soto

{"title":"TLR7 Activation in M-CSF-Dependent Monocyte-Derived Human Macrophages Potentiates Inflammatory Responses and Prompts Neutrophil Recruitment.","authors":"Miriam Simón-Fuentes, Cristina Herrero, Lucia Acero-Riaguas, Concha Nieto, Fatima Lasala, Nuria Labiod, Joanna Luczkowiak, Bárbara Alonso, Rafael Delgado, Maria Colmenares, Ángel L Corbí, Ángeles Domínguez-Soto","doi":"10.1159/000530249","DOIUrl":"10.1159/000530249","url":null,"abstract":"Toll-like receptor 7 (TLR7) is an endosomal pathogen-associated molecular pattern (PAMP) receptor that senses single-stranded RNA (ssRNA) and whose engagement results in the production of type I IFN and pro-inflammatory cytokines upon viral exposure. Recent genetic studies have established that a dysfunctional TLR7-initiated signaling is directly linked to the development of inflammatory responses. We present evidence that TLR7 is preferentially expressed by monocyte-derived macrophages generated in the presence of M-CSF (M-MØ). We now show that TLR7 activation in M-MØ triggers a weak MAPK, NFκB, and STAT1 activation and results in low production of type I IFN. Of note, TLR7 engagement reprograms MAFB+ M-MØ towards a pro-inflammatory transcriptional profile characterized by the expression of neutrophil-attracting chemokines (CXCL1-3, CXCL5, CXCL8), whose expression is dependent on the transcription factors MAFB and AhR. Moreover, TLR7-activated M-MØ display enhanced pro-inflammatory responses and a stronger production of neutrophil-attracting chemokines upon secondary stimulation. As aberrant TLR7 signaling and enhanced pulmonary neutrophil/lymphocyte ratio associate with impaired resolution of virus-induced inflammatory responses, these results suggest that targeting macrophage TLR7 might be a therapeutic strategy for viral infections where monocyte-derived macrophages exhibit a pathogenic role.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10315069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9744985","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

Tollip Inhibits IL-33 Release and Inflammation in Influenza A Virus-Infected Mouse Airways. Tollip抑制甲型流感病毒感染小鼠气道IL-33释放和炎症。

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2023-01-01 Epub Date: 2022-06-27 DOI: 10.1159/000525315

Niccolette Schaunaman, Kris Genelyn Dimasuay, Diana Cervantes, Liwu Li, Mari Numata, Monica Kraft, Hong Wei Chu

{"title":"Tollip Inhibits IL-33 Release and Inflammation in Influenza A Virus-Infected Mouse Airways.","authors":"Niccolette Schaunaman, Kris Genelyn Dimasuay, Diana Cervantes, Liwu Li, Mari Numata, Monica Kraft, Hong Wei Chu","doi":"10.1159/000525315","DOIUrl":"10.1159/000525315","url":null,"abstract":"Respiratory influenza A virus (IAV) infection continues to pose significant challenges in healthcare of human diseases including asthma. IAV infection in mice was shown to increase IL-33, a key cytokine in driving airway inflammation in asthma, but how IL-33 is regulated during viral infection remains unclear. We previously found that a genetic mutation in Toll-interacting protein (Tollip) was linked to less airway epithelial Tollip expression, increased neutrophil chemokines, and lower lung function in asthma patients. As Tollip is involved in maintaining mitochondrial function, and mitochondrial stress may contribute to extracellular ATP release and IL-33 secretion, we hypothesized that Tollip downregulates IL-33 secretion via inhibiting ATP release during IAV infection. Wild-type and Tollip knockout (KO) mice were infected with IAV and treated with either an ATP converter apyrase or an IL-33 decoy receptor soluble ST2 (sST2). KO mice significantly lost more body weight and had increased extracellular ATP, IL-33 release, and neutrophilic inflammation. Apyrase treatment reduced extracellular ATP levels, IL-33 release, and neutrophilic inflammation in Tollip KO mice. Excessive lung neutrophilic inflammation in IAV-infected Tollip KO mice was reduced by sST2, which was coupled with less IL-33 release. Our data suggest that Tollip inhibits IAV infection, potentially by inhibiting extracellular ATP release and reducing IL-33 activation and lung inflammation. In addition, sST2 may serve as a potential therapeutic approach to mitigate respiratory viral infection in human subjects with Tollip deficiency.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10643888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10317433","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: 2

Mitochondrial Damage-Associated Molecular Patterns and Metabolism in the Regulation of Innate Immunity. 线粒体损伤相关分子模式和代谢在先天免疫调节中的作用。

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2023-01-01 Epub Date: 2023-09-04 DOI: 10.1159/000533602

Yanmin Lyu, Tianyu Wang, Shuhong Huang, Zhaoqiang Zhang

{"title":"Mitochondrial Damage-Associated Molecular Patterns and Metabolism in the Regulation of Innate Immunity.","authors":"Yanmin Lyu, Tianyu Wang, Shuhong Huang, Zhaoqiang Zhang","doi":"10.1159/000533602","DOIUrl":"10.1159/000533602","url":null,"abstract":"The innate immune system, as the host's first line of defense against intruders, plays a critical role in recognizing, identifying, and reacting to a wide range of microbial intruders. There is increasing evidence that mitochondrial stress is a major initiator of innate immune responses. When mitochondria's integrity is disrupted or dysfunction occurs, the mitochondria's contents are released into the cytosol. These contents, like reactive oxygen species, mitochondrial DNA, and double-stranded RNA, among others, act as damage-related molecular patterns (DAMPs) that can bind to multiple innate immune sensors, particularly pattern recognition receptors, thereby leading to inflammation. To avoid the production of DAMPs, in addition to safeguarding organelles integrity and functionality, mitochondria may activate mitophagy or apoptosis. Moreover, mitochondrial components and specific metabolic regulations modify properties of innate immune cells. These include macrophages, dendritic cells, innate lymphoid cells, and so on, in steady state or in stimulation that are involved in processes ranging from the tricarboxylic acid cycle to oxidative phosphorylation and fatty acid metabolism. Here we provide a brief summary of mitochondrial DAMPs' initiated and potentiated inflammatory response in the innate immune system. We also provide insights into how the state of activation, differentiation, and functional polarization of innate immune cells can be influenced by alteration to the metabolic pathways in mitochondria.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/23/e7/jin-2023-0015-0001-533602.PMC10601681.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10156317","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

Mesenchymal Stromal Cells Facilitate Neutrophil-Trained Immunity by Reprogramming Hematopoietic Stem Cells. 间充质基质细胞通过重新编程造血干细胞促进中性粒细胞训练的免疫。

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2023-01-01 Epub Date: 2023-10-05 DOI: 10.1159/000533732

Julie Ng, Anna E Marneth, Alec Griffith, Daniel Younger, Sailaja Ghanta, Alan Jiao, Gareth Willis, Junwen Han, Jewel Imani, Bailin Niu, Joshua W Keegan, Brandon Hancock, Fei Guo, Yang Shi, Mark A Perrella, James A Lederer

{"title":"Mesenchymal Stromal Cells Facilitate Neutrophil-Trained Immunity by Reprogramming Hematopoietic Stem Cells.","authors":"Julie Ng, Anna E Marneth, Alec Griffith, Daniel Younger, Sailaja Ghanta, Alan Jiao, Gareth Willis, Junwen Han, Jewel Imani, Bailin Niu, Joshua W Keegan, Brandon Hancock, Fei Guo, Yang Shi, Mark A Perrella, James A Lederer","doi":"10.1159/000533732","DOIUrl":"10.1159/000533732","url":null,"abstract":"Novel therapeutics are urgently needed to prevent opportunistic infections in immunocompromised individuals undergoing cancer treatments or other immune-suppressive therapies. Trained immunity is a promising strategy to reduce this burden of disease. We previously demonstrated that mesenchymal stromal cells (MSCs) preconditioned with a class A CpG oligodeoxynucleotide (CpG-ODN), a Toll-like receptor 9 (TLR9) agonist, can augment emergency granulopoiesis in a murine model of neutropenic sepsis. Here, we used a chimeric mouse model to demonstrate that MSCs secrete paracrine factors that act on lineage-negative c-kit+ hematopoietic stem cells (HSCs), leaving them \"poised\" to enhance emergency granulopoiesis months after transplantation. Chimeric mice developed from HSCs exposed to conditioned media from MSCs and CpG-ODN-preconditioned MSCs showed significantly higher bacterial clearance and increased neutrophil granulopoiesis following lung infection than control mice. By Cleavage Under Targets and Release Using Nuclease (CUT&RUN) chromatin sequencing, we identified that MSC-conditioned media leaves H3K4me3 histone marks in HSCs at genes involved in myelopoiesis and in signaling persistence by the mTOR pathway. Both soluble factors and extracellular vesicles from MSCs mediated these effects on HSCs and proteomic analysis by mass spectrometry revealed soluble calreticulin as a potential mediator. In summary, this study demonstrates that trained immunity can be mediated by paracrine factors from MSCs to induce neutrophil-trained immunity by reprogramming HSCs for long-lasting functional changes in neutrophil-mediated antimicrobial immunity.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10622164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41140472","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

Acknowledgement to Reviewers 审稿人致谢

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2022-12-07 DOI: 10.1159/000527450

引用次数: 0

miR-142-5p Encapsulated by Serum-Derived Extracellular Vesicles Protects against Acute Lung Injury in Septic Rats following Remote Ischemic Preconditioning via the PTEN/PI3K/Akt Axis 经血清源性细胞外囊泡包封的miR-142-5p通过PTEN/PI3K/Akt轴保护脓毒症大鼠远程缺血预处理后的急性肺损伤

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2022-05-19 DOI: 10.1159/000522231

Wenliang Zhu, Xiaopei Huang, Shi-Yuan Qiu, Lingxiao Feng, Yue Wu, Huanzhang Shao

{"title":"miR-142-5p Encapsulated by Serum-Derived Extracellular Vesicles Protects against Acute Lung Injury in Septic Rats following Remote Ischemic Preconditioning via the PTEN/PI3K/Akt Axis","authors":"Wenliang Zhu, Xiaopei Huang, Shi-Yuan Qiu, Lingxiao Feng, Yue Wu, Huanzhang Shao","doi":"10.1159/000522231","DOIUrl":"https://doi.org/10.1159/000522231","url":null,"abstract":"This study intends to investigate the effects of miR-142-5p encapsulated by serum-derived extracellular vesicles (EVs) on septic acute lung injury (ALI) following remote ischemic preconditioning (RIPC) through a PTEN-involved mechanism. ALI was induced in rats by lipopolysaccharide (LPS) injection, 24 h before which RIPC was performed via the left lower limb. Next, the binding affinity between miR-142-5p and PTEN was identified. EVs were isolated from serum and injected into rats. The morphology of lung tissues, pulmonary edema, and inflammatory cell infiltration into lung tissues were then assessed, and TNF-α and IL-6 levels in serum and lung tissues were measured. The results indicated that RIPC could attenuate ALI in sepsis. miR-142-5p expression was increased in serum, lung tissues, and serum-derived EVs of ALI rats following RIPC. miR-142-5p could target PTEN to activate the PI3K/Akt signaling pathway. miR-142-5p shuttled by serum-derived EVs reduced pulmonary edema, neutrophil infiltration, and TNF-α and IL-6 levels, thus alleviating ALI in LPS-induced septic rats upon RIPC. Collectively, serum-derived EVs-loaded miR-142-5p downregulated PTEN and activated PI3K/Akt to inhibit ALI in sepsis following RIPC, thus highlighting potential therapeutic molecular targets against ALI in sepsis.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2022-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47767884","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: 1