Journal of Innate Immunity最新文献

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Role of Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 in Inflammation and Pathogen-Associated Interactions. 胶原蛋白样氧化低密度脂蛋白受体-1(LOX-1)在炎症和病原体相关相互作用中的作用。
IF 5.3 3区 医学
Journal of Innate Immunity Pub Date : 2024-01-01 Epub Date: 2024-01-17 DOI: 10.1159/000535793
Sarah Truthe, Tilman E Klassert, Stefan Schmelz, Danny Jonigk, Wulf Blankenfeldt, Hortense Slevogt
{"title":"Role of Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 in Inflammation and Pathogen-Associated Interactions.","authors":"Sarah Truthe, Tilman E Klassert, Stefan Schmelz, Danny Jonigk, Wulf Blankenfeldt, Hortense Slevogt","doi":"10.1159/000535793","DOIUrl":"10.1159/000535793","url":null,"abstract":"<p><strong>Background: </strong>Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is known as a major receptor for oxidized low-density lipoproteins (oxLDL) and plays a significant role in the genesis of atherosclerosis. Recent research has shown its involvement in cancer, ischemic stroke, and diabetes. LOX-1 is a C-type lectin receptor and is involved in the activation of immune cells and inflammatory processes. It may further interact with pathogens, suggesting a role in infections or the host's response.</p><p><strong>Summary: </strong>This review compiles the current knowledge of potential implications of LOX-1 in inflammatory processes and in host-pathogen interactions with a particular emphasis on its regulatory role in immune responses. Also discussed are genomic and structural variations found in LOX-1 homologs across different species as well as potential involvements of LOX-1 in inflammatory processes from the angle of different cell types and organ-specific interactions.</p><p><strong>Key messages: </strong>The results presented reveal both similar and different structures in human and murine LOX-1 and provide clues as to the possible origins of different modes of interaction. These descriptions raise concerns about the suitability, particularly of mouse models, that are often used in the analysis of its functionality in humans. Further research should also aim to better understand the mostly unknown binding and interaction mechanisms between LOX-1 and different pathogens. This pursuit will not only enhance our understanding of LOX-1 involvement in inflammatory processes but also identify potential targets for immunomodulatory approaches.</p>","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"105-132"},"PeriodicalIF":5.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10866614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139485735","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
Eosinophils Are an Endogenous Source of Interleukin-4 during Filarial Infections and Contribute to the Development of an Optimal T Helper 2 Response. 嗜酸性粒细胞是丝虫感染期间 IL-4 的内源性来源,有助于形成最佳的 T 辅助细胞 2 反应。
IF 5.3 3区 医学
Journal of Innate Immunity Pub Date : 2024-01-01 Epub Date: 2024-02-26 DOI: 10.1159/000536357
Cécile Guth, Pia Philippa Schumacher, Archena Vijayakumar, Hannah Borgmann, Helene Balles, Marianne Koschel, Frederic Risch, Benjamin Lenz, Achim Hoerauf, Marc P Hübner, Jesuthas Ajendra
{"title":"Eosinophils Are an Endogenous Source of Interleukin-4 during Filarial Infections and Contribute to the Development of an Optimal T Helper 2 Response.","authors":"Cécile Guth, Pia Philippa Schumacher, Archena Vijayakumar, Hannah Borgmann, Helene Balles, Marianne Koschel, Frederic Risch, Benjamin Lenz, Achim Hoerauf, Marc P Hübner, Jesuthas Ajendra","doi":"10.1159/000536357","DOIUrl":"10.1159/000536357","url":null,"abstract":"<p><strong>Introduction: </strong>Interleukin-4 (IL-4) is a central regulator of type 2 immunity, crucial for the defense against multicellular parasites like helminths. This study focuses on its roles and cellular sources during Litomosoides sigmodontis infection, a model for human filarial infections.</p><p><strong>Methods: </strong>Utilizing an IL-4 secretion assay, investigation into the sources of IL-4 during the progression of L. sigmodontis infection was conducted. The impact of eosinophils on the Th2 response was investigated through experiments involving dblGATA mice, which lack eosinophils and, consequently, eosinophil-derived IL-4.</p><p><strong>Results: </strong>The absence of eosinophils notably influenced Th2 polarization, leading to impaired production of type 2 cytokines. Interestingly, despite this eosinophil deficiency, macrophage polarization, proliferation, and antibody production remained unaffected.</p><p><strong>Conclusion: </strong>Our research uncovers eosinophils as a major source of IL-4, especially during the early phase of filarial infection. Consequently, these findings shed new light on IL-4 dynamics and eosinophil effector functions in filarial infections.</p>","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"159-172"},"PeriodicalIF":5.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10932553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139735439","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
TLRs1-10 Protein Expression in Circulating Human White Blood Cells during Bacterial and COVID-19 Infections. 细菌和 COVID-19 感染期间循环人白细胞中的 TLRs1-10 蛋白表达。
IF 4.7 3区 医学
Journal of Innate Immunity Pub Date : 2024-01-01 Epub Date: 2024-03-08 DOI: 10.1159/000536593
Louise Chomel, Mathieu Vogt, Julien Demiselle, Pierrick Le Borgne, Marine Tschirhart, Valentin Morandeau, Hamid Merdji, Laurent Miguet, Julie Helms, Ferhat Meziani, Laurent Mauvieux
{"title":"TLRs1-10 Protein Expression in Circulating Human White Blood Cells during Bacterial and COVID-19 Infections.","authors":"Louise Chomel, Mathieu Vogt, Julien Demiselle, Pierrick Le Borgne, Marine Tschirhart, Valentin Morandeau, Hamid Merdji, Laurent Miguet, Julie Helms, Ferhat Meziani, Laurent Mauvieux","doi":"10.1159/000536593","DOIUrl":"10.1159/000536593","url":null,"abstract":"<p><strong>Introduction: </strong>Toll-like receptors play crucial roles in the sepsis-induced systemic inflammatory response. Septic shock mortality correlates with overexpression of neutrophilic TLR2 and TLR9, while the role of TLR4 overexpression remains a debate. In addition, TLRs are involved in the pathogenesis of viral infections such as COVID-19, where the single-stranded RNA of SARS-CoV-2 is recognized by TLR7 and TLR8, and the spike protein activates TLR4.</p><p><strong>Methods: </strong>In this study, we conducted a comprehensive analysis of TLRs 1-10 expressions in white blood cells from 71 patients with bacterial and viral infections. Patients were divided into 4 groups based on disease type and severity (sepsis, septic shock, moderate, and severe COVID-19) and compared to 7 healthy volunteers.</p><p><strong>Results: </strong>We observed a significant reduction in the expression of TLR4 and its co-receptor CD14 in septic shock neutrophils compared to the control group (p &lt; 0.001). Severe COVID-19 patients exhibited a significant increase in TLR3 and TLR7 levels in neutrophils compared to controls (p &lt; 0.05). Septic shock patients also showed a similar increase in TLR7 in neutrophils along with elevated intermediate monocytes (CD14+CD16+) compared to the control group (p &lt; 0.005 and p &lt; 0.001, respectively). However, TLR expression remained unchanged in lymphocytes.</p><p><strong>Conclusion: </strong>This study provides further insights into the mechanisms of TLR activation in various infectious conditions. Additional analysis is needed to assess their correlation with patient outcome and to evaluate the impact of TLR-pathway modulation during septic shock and severe COVID-19.</p>","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"216-225"},"PeriodicalIF":4.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11001289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140094203","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
Association of Vitamin D with Severity and Outcome of COVID-19: Clinical and Experimental Evidence. 维生素D与COVID-19严重程度和结局的关系:临床和实验证据
IF 5.3 3区 医学
Journal of Innate Immunity Pub Date : 2024-01-01 Epub Date: 2023-11-26 DOI: 10.1159/000535302
Georgios Renieris, Spyros Foutadakis, Theano Andriopoulou, Victoria-Marina Spanou, Dionyssia-Eirini Droggiti, Dionysios Kafousopoulos, Theologia Gkavogianni, Georgia Damoraki, Giannis Vatsellas, Evangelos J Giamarellos-Bourboulis
{"title":"Association of Vitamin D with Severity and Outcome of COVID-19: Clinical and Experimental Evidence.","authors":"Georgios Renieris, Spyros Foutadakis, Theano Andriopoulou, Victoria-Marina Spanou, Dionyssia-Eirini Droggiti, Dionysios Kafousopoulos, Theologia Gkavogianni, Georgia Damoraki, Giannis Vatsellas, Evangelos J Giamarellos-Bourboulis","doi":"10.1159/000535302","DOIUrl":"10.1159/000535302","url":null,"abstract":"<p><strong>Introduction: </strong>The role of vitamin in COVID-19 remains controversial. We investigated the association between endogenous vitamin D and the severity of COVID-19 as well as the mechanisms of action of vitamin D supplementation.</p><p><strong>Methods: </strong>25(OH)D3 in serum was associated with disease severity and outcome in 190 COVID-19 patients. In a COVID-19 animal model using intravenous injection of plasma from patients with COVID-19 acute respiratory distress syndrome into C57/BL6 mice, mice were treated with 0.25 μg human 1,25(OH)D3 or vehicle. Mice were sacrificed on day 4. Cytokines and myeloperoxidase (MPO) in tissues were measured. Changes in gene expression after vitamin D supplementation were measured.</p><p><strong>Results: </strong>Vitamin D deficiency and insufficiency were associated with increased severity and unfavorable outcome after 28 days. Vitamin D levels were negatively associated with biomarkers of COVID-19 severity. Vitamin D supplementation after challenge of mice with COVID-19 plasma led to reduced levels of TNFα, IL-6, IFNγ, and MPO in the lung, as well as down-regulation of pro-inflammatory pathways.</p><p><strong>Conclusion: </strong>Normal levels of endogenous vitamin D are associated with reduced severity and risk of unfavorable outcome in COVID-19, possibly through attenuation of tissue-specific hyperinflammation.</p>","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"1-11"},"PeriodicalIF":5.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10764091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138440779","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
C-X-C motif chemokine ligand 1 promotes colitis by modulating the gut microbiota C-X-C motif趋化因子配体 1 通过调节肠道微生物群促进结肠炎的发生
IF 5.3 3区 医学
Journal of Innate Immunity Pub Date : 2023-12-08 DOI: 10.1159/000535637
Hang Zhao, Wenhua Li, Xin Zhou, Liang Pan, Yun Feng, Pingyu Gao, Jie Ji, Huanyan Zhang, Kai Zhao, Chi Wang, Zhanjun Lu
{"title":"C-X-C motif chemokine ligand 1 promotes colitis by modulating the gut microbiota","authors":"Hang Zhao, Wenhua Li, Xin Zhou, Liang Pan, Yun Feng, Pingyu Gao, Jie Ji, Huanyan Zhang, Kai Zhao, Chi Wang, Zhanjun Lu","doi":"10.1159/000535637","DOIUrl":"https://doi.org/10.1159/000535637","url":null,"abstract":"Introduction: C-X-C motif chemokine ligand 1 (CXCL1) is a potent neutrophil chemoattractant that plays a pivotal role in recruiting neutrophils during inflammatory conditions. This study explored the role of CXCL1 in modulating the gut microbiota, influencing neutrophil infiltration, and contributing to the development of colitis. \u0000Methods: We employed quantitative PCR to assess CXCL1 expression in colon samples. A mouse model of DSS-induced colitis was utilized to explore the progression of colitis in wild-type (WT) and CXCL1-deficient (CXCL1-/-) mice. \u0000Results: Colitis attenuation was evident in CXCL1-/- mice. Significant alterations were observed in the gut microbiome, as revealed by 16S rRNA gene sequencing. Furthermore, CXCL1-/- mice exhibited reduced gut permeability and diminished endotoxin levels in peripheral blood following DSS treatment compared to WT mice. In response to DSS treatment, WT mice showed a clear increase in neutrophil infiltration, while CXCL1-/- mice exhibited lower levels of infiltration. FMT using stools from CXCL1-/- mice alleviated DSS-induced colitis. Interestingly, FMT from patients with colitis increased CXCL1 and Ly6G expression in colons of gut-sterilized mice. Clinical data analysis revealed elevated CXCL1 and CD15 expression in patients with colitis, with a positive correlation between the severity of colitis and the expression of CXCL1 and CD15. \u0000Conclusion: These findings shed light on the pivotal role of CXCL1 in promoting colitis by modulating the gut microbiota.\u0000","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":"53 30","pages":""},"PeriodicalIF":5.3,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138587955","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
Erratum. 勘误表。
IF 5.3 3区 医学
Journal of Innate Immunity Pub Date : 2023-05-15 DOI: 10.1159/000530893
{"title":"Erratum.","authors":"","doi":"10.1159/000530893","DOIUrl":"https://doi.org/10.1159/000530893","url":null,"abstract":"Geburtshilfe und Frauenheilkunde 48 (1988) , (Heft 6/88) P. Wieacker, P. Peters, M. Breckwoldt: Gonnadotropinresistenz beim Rothmund-Thomson-Syndrom","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":"15 1","pages":"516"},"PeriodicalIF":5.3,"publicationDate":"2023-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9663774","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
Serine Protease Networks Mediate Immune Responses in Extra-Embryonic Tissues of Eggs in the Tobacco Hornworm, Manduca sexta. 丝氨酸蛋白酶网络介导烟草角虫卵胚外组织的免疫应答。
IF 5.3 3区 医学
Journal of Innate Immunity Pub Date : 2023-01-01 Epub Date: 2022-12-13 DOI: 10.1159/000527974
Tisheng Shan, Yang Wang, Neal T Dittmer, Michael R Kanost, Haobo Jiang
{"title":"Serine Protease Networks Mediate Immune Responses in Extra-Embryonic Tissues of Eggs in the Tobacco Hornworm, Manduca sexta.","authors":"Tisheng Shan, Yang Wang, Neal T Dittmer, Michael R Kanost, Haobo Jiang","doi":"10.1159/000527974","DOIUrl":"10.1159/000527974","url":null,"abstract":"<p><p>The melanization and Toll pathways, regulated by a network of serine proteases and noncatalytic serine protease homologs (SPHs), have been investigated mostly in adult and larval insects. However, how these innate immune reactions are regulated in insect eggs remains unclear. Here we present evidence from transcriptome and proteome analyses that extra-embryonic tissues (yolk and serosa) of early-stage Manduca sexta eggs are immune competent, with expression of immune effector genes including prophenoloxidase and antimicrobial peptides. We identified gene products of the melanization and Toll pathways in M. sexta eggs. Through in vitro reconstitution experiments, we demonstrated that constitutive and infection-induced serine protease cascade modules that stimulate immune responses exist in the extra-embryonic tissues of M. sexta eggs. The constitutive module (HP14b-SP144-GP6) may promote rapid early immune signaling by forming a cascade activating the cytokine Spätzle and regulating melanization by activating prophenoloxidase (proPO). The inducible module (HP14a-HP21-HP5) may trigger enhanced activation of Spätzle and proPO at a later phase of infection. Crosstalk between the two modules may occur in transition from the constitutive to the induced response in eggs inoculated with bacteria. Examination of data from two other well-studied insect species, Tribolium castaneum and Drosophila melanogaster, supports a role for a serosa-dependent constitutive protease cascade in protecting early embryos against invading pathogens.</p>","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"365-379"},"PeriodicalIF":5.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10643904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10493118","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
Immunothrombosis and Complement Activation Contribute to Disease Severity and Adverse Outcome in COVID-19. 免疫血栓形成和补体激活会导致新冠肺炎的疾病严重程度和不良后果。
IF 5.3 3区 医学
Journal of Innate Immunity Pub Date : 2023-01-01 Epub Date: 2023-11-08 DOI: 10.1159/000533339
Tiphaine Ruggeri, Yasmin De Wit, Noëlia Schärz, Gerard van Mierlo, Anne Angelillo-Scherrer, Justine Brodard, Joerg C Schefold, Cédric Hirzel, Ilse Jongerius, Sacha Zeerleder
{"title":"Immunothrombosis and Complement Activation Contribute to Disease Severity and Adverse Outcome in COVID-19.","authors":"Tiphaine Ruggeri, Yasmin De Wit, Noëlia Schärz, Gerard van Mierlo, Anne Angelillo-Scherrer, Justine Brodard, Joerg C Schefold, Cédric Hirzel, Ilse Jongerius, Sacha Zeerleder","doi":"10.1159/000533339","DOIUrl":"10.1159/000533339","url":null,"abstract":"<p><p>Severe COVID-19 is characterized by systemic inflammation and multiple organ dysfunction syndrome (MODS). Arterial and venous thrombosis are involved in the pathogenesis of MODS and fatality in COVID-19. There is evidence that complement and neutrophil activation in the form of neutrophil extracellular traps are main drivers for development of microvascular complications in COVID-19. Plasma and serum samples were collected from 83 patients infected by SARS-CoV-2 during the two first waves of COVID-19, before the availability of SARS-CoV-2 vaccination. Samples were collected at enrollment, day 11, and day 28; and patients had differing severity of disease. In this comprehensive study, we measured cell-free DNA, neutrophil activation, deoxyribonuclease I activity, complement activation, and D-dimers in longitudinal samples of COVID-19 patients. We show that all the above markers, except deoxyribonuclease I activity, increased with disease severity. Moreover, we provide evidence that in severe disease there is continued neutrophil and complement activation, as well as D-dimer formation and nucleosome release, whereas in mild and moderate disease all these markers decrease over time. These findings suggest that neutrophil and complement activation are important drivers of microvascular complications and that they reflect immunothrombosis in these patients. Neutrophil activation, complement activation, cell-free DNA, and D-dimer levels have the potential to serve as reliable biomarkers for disease severity and fatality in COVID-19. They might also serve as suitable markers with which to monitor the efficacy of therapeutic interventions in COVID-19.</p>","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"850-864"},"PeriodicalIF":5.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10699833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71521679","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
Perilipin 1 Deficiency Prompts Lipolysis in Lipid Droplets and Aggravates the Pathogenesis of Persistent Immune Activation in Drosophila. 脂周蛋白1缺乏促进脂滴的脂解,并加重果蝇持续免疫激活的发病机制。
IF 5.3 3区 医学
Journal of Innate Immunity Pub Date : 2023-01-01 Epub Date: 2023-09-23 DOI: 10.1159/000534099
Lei Wang, Jiaxin Lin, Kaiyan Yang, Weina Wang, Yan Lv, Xiangkang Zeng, Yaya Zhao, Junjing Yu, Lei Pan
{"title":"Perilipin 1 Deficiency Prompts Lipolysis in Lipid Droplets and Aggravates the Pathogenesis of Persistent Immune Activation in Drosophila.","authors":"Lei Wang, Jiaxin Lin, Kaiyan Yang, Weina Wang, Yan Lv, Xiangkang Zeng, Yaya Zhao, Junjing Yu, Lei Pan","doi":"10.1159/000534099","DOIUrl":"10.1159/000534099","url":null,"abstract":"<p><p>Lipid droplets (LDs) are highly dynamic intracellular organelles, which are involved in lots of biological processes. However, the dynamic morphogenesis and functions of intracellular LDs during persistent innate immune responses remain obscure. In this study, we induce long-term systemic immune activation in Drosophila through genetic manipulation. Then, the dynamic pattern of LDs is traced in the Drosophila fat body. We find that deficiency of Plin1, a key regulator of LDs' reconfiguration, blocks LDs minimization at the initial stage of immune hyperactivation but enhances LDs breakdown at the later stage of sustained immune activation via recruiting the lipase Brummer (Bmm, homologous to human ATGL). The high wasting in LDs shortens the lifespan of flies with high-energy-cost immune hyperactivation. Therefore, these results suggest a critical function of LDs during long-term immune activation and provide a potential treatment for the resolution of persistent inflammation.</p>","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"697-708"},"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/4d/d4/jin-2023-0015-0001-534099.PMC10601664.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41114840","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
Inhibition of Piezo1 Ameliorates Intestinal Inflammation and Limits the Activation of Group 3 Innate Lymphoid Cells in Experimental Colitis. 在实验性结肠炎中,抑制Piezo1可改善肠道炎症并限制第3组固有淋巴细胞的激活。
IF 5.3 3区 医学
Journal of Innate Immunity Pub Date : 2023-01-01 Epub Date: 2023-09-19 DOI: 10.1159/000533525
Chang Liu, Yanan Xia, Shichen Fu, Fanyi Meng, Bingcheng Feng, Leiqi Xu, Lixiang Li, Xiuli Zuo
{"title":"Inhibition of Piezo1 Ameliorates Intestinal Inflammation and Limits the Activation of Group 3 Innate Lymphoid Cells in Experimental Colitis.","authors":"Chang Liu, Yanan Xia, Shichen Fu, Fanyi Meng, Bingcheng Feng, Leiqi Xu, Lixiang Li, Xiuli Zuo","doi":"10.1159/000533525","DOIUrl":"10.1159/000533525","url":null,"abstract":"<p><p>Piezo1, the mechanosensory ion channel, has attracted increasing attention for its essential roles in various inflammatory responses and immune-related diseases. Although most of the key immune cells in inflammatory bowel disease (IBD) have been reported to be regulated by Piezo1, the specific role of Piezo1 in colitis has yet to be intensively studied. The present study investigated the impact of pharmacological inhibition of Piezo1 on dextran sulfate sodium (DSS)-induced colitis and explored the role of Piezo1 in intestinal immune cells in the context of colitis. We observed upregulated expression of Piezo1 in the colon tissue of mice with DSS-induced colitis. Pharmacological inhibition of Piezo1 by GsMTx4 diminished the severity of colitis. Piezo1 inhibition downregulated the expression of pro-inflammatory mediators Il1b, Il6, and Ptgs2 in colonic tissue and suppressed the production of IL-6 from macrophages and dendritic cells without altering the balance of T helper (Th) cells. In particular, Piezo1 did not affect cell viability but regulated cell proliferation and production of IL-17A in group 3 innate lymphoid cells (ILC3s), which is dependent on the PI3K-Akt-mTOR signaling pathway. Our findings uncover Piezo1 as an effective regulator of gut inflammation. Targeting Piezo1 could be a promising strategy to modulate intestinal immunity in IBD.</p>","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"709-723"},"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/84/c3/jin-2023-0015-0001-533525.PMC10601687.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41124956","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
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