Journal of immunology最新文献

Immunometabolic Mechanisms of LANCL2 in CD4+ T Cells and Phagocytes Provide Protection from Systemic Lupus Erythematosus. CD4+ T细胞和吞噬细胞中的LANCL2免疫代谢机制提供了对系统性红斑狼疮的保护

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-10-04 DOI: 10.4049/jimmunol.2400127

Andrew Leber, Raquel Hontecillas, Nuria Tubau-Juni, Sarah N Fitch, Josep Bassaganya-Riera

{"title":"Immunometabolic Mechanisms of LANCL2 in CD4+ T Cells and Phagocytes Provide Protection from Systemic Lupus Erythematosus.","authors":"Andrew Leber, Raquel Hontecillas, Nuria Tubau-Juni, Sarah N Fitch, Josep Bassaganya-Riera","doi":"10.4049/jimmunol.2400127","DOIUrl":"https://doi.org/10.4049/jimmunol.2400127","url":null,"abstract":"Lanthionine synthetase C-like 2 (LANCL2) is an immunoregulatory therapeutic target for autoimmune diseases. NIM-1324 is an investigational new drug aimed at addressing the unmet clinical needs of patients with systemic lupus erythematosus (SLE) by targeting the LANCL2 immunometabolic pathway. In R848 and bm12 adoptive transfer models of systemic inflammation that share pathologies with SLE, Lancl2-/- mice experienced greater mortality, increased spleen weight, and reduced CD25hi FOXP3+ CD4+ regulatory T cells compared with the wild type. Conversely, treatment with NIM-1324 in the wild type increased CD25hi FOXP3+ regulatory T cells while reducing inflammatory IL-17+ and IL-21+ CD4+ T cell subsets in the spleen. In traditional mouse models of SLE (NZB/W F1 and MRL/lpr), oral treatment with NIM-1324 protected against weight loss and proteinuria, decreased anti-dsDNA titers, and provided similar changes to the CD4+ T cell compartment in the spleen. The pharmacological activation of LANCL2 by NIM-1324 rescued hypocomplementemia, reduced kidney histopathological scores, and decreased blood IFN response genes and inflammatory cytokines. The loss of LANCL2 in phagocytes impairs phagosome processing, leading to increased uptake of material and inflammatory cytokine production, yet decreased markers of endosomal maturation, phagosome turnover, and lysozyme activity. Treatment with NIM-1324 increases metabolic and lysozyme activity in the phagosome, providing support for increased markers of early phagosome function. This efficacy translated to human PBMCs from patients with SLE, because ex vivo treatment with NIM-1324 resulted in reduced levels of IFN-α, IL-6, and IL-8. Consequently, the activation of LANCL2 effectively modulates CD4+ T cell differentiation and phagocyte activation, supporting immune tolerance in SLE.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372055","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

Cell-surface Milieu Remodeling in Human Dendritic Cell Activation. 人类树突状细胞活化过程中的细胞表面环境重塑

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-10-01 DOI: 10.4049/jimmunol.2400089

Namrata D Udeshi, Charles Xu, Zuzhi Jiang, Shihong Max Gao, Qian Yin, Wei Luo, Steven A Carr, Mark M Davis, Jiefu Li

{"title":"Cell-surface Milieu Remodeling in Human Dendritic Cell Activation.","authors":"Namrata D Udeshi, Charles Xu, Zuzhi Jiang, Shihong Max Gao, Qian Yin, Wei Luo, Steven A Carr, Mark M Davis, Jiefu Li","doi":"10.4049/jimmunol.2400089","DOIUrl":"10.4049/jimmunol.2400089","url":null,"abstract":"Dendritic cells (DCs) are specialized sentinel and APCs coordinating innate and adaptive immunity. Through proteins on their cell surface, DCs sense changes in the environment, internalize pathogens, present processed Ags, and communicate with other immune cells. By combining chemical labeling and quantitative mass spectrometry, we systematically profiled and compared the cell-surface proteomes of human primary conventional DCs (cDCs) in their resting and activated states. TLR activation by a lipopeptide globally reshaped the cell-surface proteome of cDCs, with >100 proteins upregulated or downregulated. By simultaneously elevating positive regulators and reducing inhibitory signals across multiple protein families, the remodeling creates a cell-surface milieu promoting immune responses. Still, cDCs maintain the stimulatory-to-inhibitory balance by leveraging a distinct set of inhibitory molecules. This analysis thus uncovers the molecular complexity and plasticity of the cDC cell surface and provides a roadmap for understanding cDC activation and signaling.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11408084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916926","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

Microbe-binding Antibodies in the Female Genital Tract: Associations with the Vaginal Microbiome and Genital Immunology. 女性生殖道中的微生物结合抗体：与阴道微生物组和生殖道免疫学的关联。

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-09-30 DOI: 10.4049/jimmunol.2400233

Rachel Liu, James Pollock, Sanja Huibner, Suji Udayakumar, Erastus Irungu, Pauline Ngurukiri, Peter Muthoga, Wendy Adhiambo, Joshua Kimani, Tara Beattie, Bryan Coburn, Rupert Kaul

{"title":"Microbe-binding Antibodies in the Female Genital Tract: Associations with the Vaginal Microbiome and Genital Immunology.","authors":"Rachel Liu, James Pollock, Sanja Huibner, Suji Udayakumar, Erastus Irungu, Pauline Ngurukiri, Peter Muthoga, Wendy Adhiambo, Joshua Kimani, Tara Beattie, Bryan Coburn, Rupert Kaul","doi":"10.4049/jimmunol.2400233","DOIUrl":"https://doi.org/10.4049/jimmunol.2400233","url":null,"abstract":"Bacteria-Ig interactions maintain homeostasis in the gut through the clearance of pathogenic bacteria and the development of immune tolerance to inflammatory bacteria; whether similar interactions modulate inflammation and bacterial colonization in the female genital tract is uncertain. In this study, we used a flow cytometry-based assay to quantify microbe-binding IgA and IgG in the cervicovaginal secretions of 200 HIV-uninfected women from Nairobi, Kenya that were enriched for bacterial vaginosis. Total IgA and IgG were abundant and frequently demonstrated ex vivo binding to the key vaginal bacteria species Gardnerella vaginalis, Prevotella bivia, Lactobacillus iners, and Lactobacillus crispatus, which are largely microbe-specific. Microbe-binding Abs were generally not associated with the presence or abundance of their corresponding bacteria. Total and microbe-binding IgA and IgG were inversely correlated with total bacterial abundance and positively correlated with several proinflammatory cytokines (IL-6, TNF) and chemotactic chemokines (IP-10, MIG, MIP-1α, MIP-1β, MIP-3α, MCP-1, IL-8), independent of total bacterial abundance. Flow cytometry-based quantification of microbe-binding Abs provides a platform to investigate host-microbiota interactions in the female genital tract of human observational and interventional studies. In contrast to the gut, cervicovaginal microbe-binding IgA and IgG do not appear to be immunoregulatory but may indirectly mitigate bacteria-induced inflammation by reducing total bacterial abundance.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348205","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

Tim-3 Is Required for Regulatory T Cell-Mediated Promotion of T Cell Exhaustion and Viral Persistence during Chronic Lymphocytic Choriomeningitis Virus Infection. 在慢性淋巴细胞性脉络膜脑膜炎病毒感染过程中，Tim-3 是调节性 T 细胞介导的促进 T 细胞衰竭和病毒持续存在所必需的。

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-09-30 DOI: 10.4049/jimmunol.2400119

Hector M Nieves-Rosado, Hridesh Banerjee, Angela Gocher-Demske, Priyanka Manandhar, Isha Mehta, Ogechukwu Ezenwa, Bingxian Xie, Ben Murter, Jishnu Das, Dario A A Vignali, Greg M Delgoffe, Lawrence P Kane

{"title":"Tim-3 Is Required for Regulatory T Cell-Mediated Promotion of T Cell Exhaustion and Viral Persistence during Chronic Lymphocytic Choriomeningitis Virus Infection.","authors":"Hector M Nieves-Rosado, Hridesh Banerjee, Angela Gocher-Demske, Priyanka Manandhar, Isha Mehta, Ogechukwu Ezenwa, Bingxian Xie, Ben Murter, Jishnu Das, Dario A A Vignali, Greg M Delgoffe, Lawrence P Kane","doi":"10.4049/jimmunol.2400119","DOIUrl":"https://doi.org/10.4049/jimmunol.2400119","url":null,"abstract":"Expression of T cell Ig and mucin domain-containing protein 3 (Tim-3) is upregulated on regulatory T cells (Tregs) during chronic viral infections. In several murine and human chronic infections, the expression of Tim-3 is associated with poor control of viral burden and impaired antiviral immune responses. However, the role of Tim-3+ Tregs during persistent viral infections has not been fully defined. We employed an inducible Treg-specific Tim-3 loss-of-function (Tim-3 Treg knockout) murine model to dissect the role of Tim-3 on Tregs during chronic lymphocytic choriomeningitis virus infection. Tim-3 Treg knockout mice exhibited a decrease in morbidity, a more potent virus-specific T cell response, and a significant decrease in viral burden. These mice also had a reduction in the frequency of PD-1+Tim-3+ and PD-1+Tox+ gp33-specific exhausted CD8+ T cells. Our findings demonstrate that modulation of a single surface protein on Tregs can lead to a reduction in viral burden, limit T cell exhaustion, and enhance gp33-specific T cell response. These studies may help to identify Tim-3-directed therapies for the management of persistent infections and cancer.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348207","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

Integrins α5β1 and αvβ3 Differentially Participate in the Recruitment and Reprogramming of Tumor-associated Macrophages in the In Vitro and In Vivo Models of Breast Tumor. 整合素α5β1和αvβ3在体外和体内乳腺肿瘤模型中不同程度地参与了肿瘤相关巨噬细胞的招募和重编程。

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-09-27 DOI: 10.4049/jimmunol.2400180

Nibedita Dalpati, Shubham Kumar Rai, Shiba Prasad Dash, Puneet Kumar, Divya Singh, Pranita P Sarangi

{"title":"Integrins α5β1 and αvβ3 Differentially Participate in the Recruitment and Reprogramming of Tumor-associated Macrophages in the In Vitro and In Vivo Models of Breast Tumor.","authors":"Nibedita Dalpati, Shubham Kumar Rai, Shiba Prasad Dash, Puneet Kumar, Divya Singh, Pranita P Sarangi","doi":"10.4049/jimmunol.2400180","DOIUrl":"https://doi.org/10.4049/jimmunol.2400180","url":null,"abstract":"Tumor-associated macrophages (TAMs) drive the protumorigenic responses and facilitate tumor progression via matrix remodeling, angiogenesis, and immunosuppression by interacting with extracellular matrix proteins via integrins. However, the expression dynamics of integrin and its correlation with TAM functional programming in the tumors remain unexplored. In this study, we examined surface integrins' role in TAM recruitment and phenotypic programming in a 4T1-induced murine breast tumor model. Our findings show that integrin α5β1 is upregulated in CD11b+Ly6Chi monocytes in the bone marrow and blood by day 10 after tumor induction. Subsequent analysis revealed elevated integrin α5β1 expression on tumor-infiltrating monocytes (Ly6ChiMHC class II [MHCII]low) and M1 TAMs (F4/80+Ly6ClowMHCIIhi), whereas integrin αvβ3 was predominantly expressed on M2 TAMs (F4/80+Ly6ClowMHCIIlow), correlating with higher CD206 and MERTK expression. Gene profiling of cells sorted from murine tumors showed that CD11b+Ly6G-F4/80+α5+ TAMs had elevated inflammatory genes (IL-6, TNF-α, and STAT1/2), whereas CD11b+Ly6G-F4/80+αv+ TAMs exhibited a protumorigenic phenotype (IL-10, Arg1, TGF-β, and STAT3/6). In vitro studies demonstrated that blocking integrin α5 and αv during macrophage differentiation from human peripheral blood monocytes reduced cell spreading and expression of CD206 and CD163 in the presence of specific matrix proteins, fibronectin, and vitronectin. Furthermore, RNA sequencing data analysis (GEO dataset: GSE195857) from bone marrow-derived monocytes and TAMs in 4T1 mammary tumors revealed differential integrin α5 and αv expression and their association with FAK and SRC kinase. In line with this, FAK inhibition during TAM polarization reduced SRC, STAT1, and STAT6 phosphorylation. In conclusion, these findings underscore the crucial role of integrins in TAM recruitment, polarization, and reprogramming in tumors.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348204","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 G Protein-Coupled Receptor GPR56 Is an Inhibitory Checkpoint for NK Cell Migration. G 蛋白偶联受体 GPR56 是 NK 细胞迁移的抑制性检查点

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-09-25 DOI: 10.4049/jimmunol.2400228

Daniel Palacios, Rakesh Kumar Majhi, Edina K Szabo, Dennis Clement, Mieszko Lachota, Herman Netskar, Leena Penna, Silje Z Krokeide, Marianna Vincenti, Lise Kveberg, Karl-Johan Malmberg

{"title":"The G Protein-Coupled Receptor GPR56 Is an Inhibitory Checkpoint for NK Cell Migration.","authors":"Daniel Palacios, Rakesh Kumar Majhi, Edina K Szabo, Dennis Clement, Mieszko Lachota, Herman Netskar, Leena Penna, Silje Z Krokeide, Marianna Vincenti, Lise Kveberg, Karl-Johan Malmberg","doi":"10.4049/jimmunol.2400228","DOIUrl":"https://doi.org/10.4049/jimmunol.2400228","url":null,"abstract":"G protein-coupled receptors (GPCRs) represent the largest family of surface receptors and are responsible for key physiological functions, including cell growth, neurotransmission, hormone release, and cell migration. The GPCR 56 (GPR56), encoded by ADGRG1, is an adhesion GPCR found on diverse cell types, including neural progenitor cells, melanoma cells, and lymphocytes, such as effector memory T cells, γδ T cells, and NK cells. Using RNA-sequencing and high-resolution flow cytometry, we found that GPR56 mRNA and protein expression increased with NK cell differentiation, reaching its peak in adaptive NK cells. Small interfering RNA silencing of GPR56 led to increased spontaneous and chemokine-induced migration, suggesting that GPR56 functions as an upstream checkpoint for migration of highly differentiated NK cells. Increased NK cell migration could also be induced by agonistic stimulation of GPR56 leading to rapid internalization and deactivation of the receptor. Mechanistically, GPR56 ligation and downregulation were associated with transcriptional coactivator with PDZ-binding motif translocation to the nucleus and increased actin polymerization. Together, these data provide insights into the role of GPR56 in the migratory behavior of human NK cell subsets and may open possibilities to improve NK cell infiltration into cancer tissues by releasing a migratory checkpoint.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348206","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

Developmental Vitamin D Deficiency and the Vitamin D Receptor Control Hematopoiesis. 发育期维生素 D 缺乏和维生素 D 受体控制造血功能

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-09-25 DOI: 10.4049/jimmunol.2400292

Juhi Arora, Nicole E Froelich, Mengzhu Tang, Veronika Weaver, Robert F Paulson, Margherita T Cantorna

{"title":"Developmental Vitamin D Deficiency and the Vitamin D Receptor Control Hematopoiesis.","authors":"Juhi Arora, Nicole E Froelich, Mengzhu Tang, Veronika Weaver, Robert F Paulson, Margherita T Cantorna","doi":"10.4049/jimmunol.2400292","DOIUrl":"https://doi.org/10.4049/jimmunol.2400292","url":null,"abstract":"Vitamin D status, the vitamin D receptor (VDR), and the ability to produce active vitamin D [1,25(OH)2D, regulated by Cyp27b1] regulate fetal and adult hematopoiesis. Transgenic reporter mice that express the tdTomato RFP as an indication of Vdr expression were used to identify immune cells that express the Vdr. Vdr/tdTomato+ hematopoietic progenitors were identified as early as embryonic day (E)15.5, establishing that these cells have expressed the Vdr and are vitamin D targets. Maternal vitamin D deficiency [D-; serum 25(OH)D < 20 ng/ml] or Vdr knockout or Cyp27b1 knockout resulted in embryos with fewer fetal progenitors. Vdr/tdTomato+ expression was found to increase with age in CD8+ T cells and innate lymphoid cells (ILCs)1 and ILC3, suggesting that initial Vdr expression in these cells is dependent on environmental factors immediately postbirth. In adult tissues, the frequencies of mature T cells and ILCs as well as Vdr/tdTomato expression were reduced by D-. Maternal D- resulted in fewer progenitors that expressed Vdr/tdTomato+ at E15.5 and fewer Vdr/tdTomato+ immune cells in the adult spleen than offspring from D+ mice. We challenged D- mice with H1N1 influenza infection and found that D- mice were more susceptible than D+ mice. Treating D- mice with vitamin D restored Vdr/tdTomato+ expression in splenic T cells and partially restored resistance to H1N1 infection, which shows that developmental D- results in lingering effects on Vdr expression in the adult immune system that compromise the immune response to H1N1 infection. Vitamin D and the Vdr regulate hematopoiesis in both fetal and postnatal phases of immune cell development that impact the immune response to a viral infection.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348193","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

MARCH8 Mediates K27-Linked Polyubiquitination of IL-7 Receptor α to Negatively Regulate IL-7-Triggered T Cell Homeostasis. MARCH8 介导 IL-7 受体 α 的 K27 链接多泛素化，从而负向调节 IL-7 触发的 T 细胞稳态。

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-09-23 DOI: 10.4049/jimmunol.2400253

Deng Gao, Xue-Mei Yi, Lu Feng, Shu Li, Hong-Bing Shu

{"title":"MARCH8 Mediates K27-Linked Polyubiquitination of IL-7 Receptor α to Negatively Regulate IL-7-Triggered T Cell Homeostasis.","authors":"Deng Gao, Xue-Mei Yi, Lu Feng, Shu Li, Hong-Bing Shu","doi":"10.4049/jimmunol.2400253","DOIUrl":"https://doi.org/10.4049/jimmunol.2400253","url":null,"abstract":"IL-7 is a cytokine produced by stromal cells, which binds to IL-7Rα and plays an important role for homeostasis of T lymphocytes. Excessive activities of IL-7-triggered signaling pathways causes autoimmune diseases. How IL-7-triggered signaling and immune effects are regulated is not fully understood. In this study, we show that the membrane-associated RING-CH (MARCH) E3 ligase family member MARCH8 mediates K27-linked polyubiquitination of IL-7Rα, leading to its lysosomal degradation. Site-directed mutagenesis suggests that MARCH8 meditates polyubiquitination of IL-7Rα at K265/K266, and mutation of these residues renders IL-7Rα resistance to MARCH8-mediated polyubiquitination and degradation. MARCH8 deficiency increases IL-7-triggered activation of the downstream transcription factor STAT5 and transcriptional induction of the effector genes in human T lymphoma cells. MARCH8 deficiency also promotes IL-7-triggered T cell proliferation and splenic memory CD8+ T cell differentiation in mice. Our findings suggest that MARCH8 negatively regulates IL-7-triggered signaling by mediating K27-linked polyubiquitination and lysosomal degradation of IL-7Rα, which reveals a negative regulatory mechanism of IL-7-triggered T cell homeostasis.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289202","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

Intravenous Bacillus Calmette-Guérin (BCG) Induces a More Potent Airway and Lung Immune Response than Intradermal BCG in Simian Immunodeficiency Virus-infected Macaques. 与皮内卡介苗相比，静脉注射卡介苗（Bacillus Calmette-Guérin，BCG）能在猿免疫缺陷病毒感染的猕猴中诱导更强的气道和肺部免疫反应。

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-09-23 DOI: 10.4049/jimmunol.2400417

Solomon Jauro, Erica C Larson, Janelle L Gleim, Brendon M Wahlberg, Mark A Rodgers, Julia C Chehab, Alondra E Lopez-Velazques, Cassaundra L Ameel, Jaime A Tomko, Jennifer L Sakal, Todd DeMarco, H Jacob Borish, Pauline Maiello, E Lake Potter, Mario Roederer, Philana Ling Lin, JoAnne L Flynn, Charles A Scanga

{"title":"Intravenous Bacillus Calmette-Guérin (BCG) Induces a More Potent Airway and Lung Immune Response than Intradermal BCG in Simian Immunodeficiency Virus-infected Macaques.","authors":"Solomon Jauro, Erica C Larson, Janelle L Gleim, Brendon M Wahlberg, Mark A Rodgers, Julia C Chehab, Alondra E Lopez-Velazques, Cassaundra L Ameel, Jaime A Tomko, Jennifer L Sakal, Todd DeMarco, H Jacob Borish, Pauline Maiello, E Lake Potter, Mario Roederer, Philana Ling Lin, JoAnne L Flynn, Charles A Scanga","doi":"10.4049/jimmunol.2400417","DOIUrl":"10.4049/jimmunol.2400417","url":null,"abstract":"Tuberculosis (TB), caused by Mycobacterium tuberculosis, is one of the leading causes of death due to an infectious agent. Coinfection with HIV exacerbates M. tuberculosis infection outcomes in people living with HIV. Bacillus Calmette-Guérin (BCG), the only approved TB vaccine, is effective in infants, but its efficacy in adolescents and adults is limited. In this study, we investigated the immune responses elicited by BCG administered via i.v. or intradermal (i.d.) routes in SIV-infected Mauritian cynomolgus macaques (MCM) without the confounding effects of M. tuberculosis challenge. We assessed the impact of vaccination on T cell responses in the airway, blood, and tissues (lung, thoracic lymph nodes, and spleen), as well as the expression of cytokines, cytotoxic effectors, and key transcription factors. Our results showed that i.v. BCG induces a robust and sustained immune response, including tissue-resident memory T cells in lungs, polyfunctional CD4+ and CD8αβ+ T cells expressing multiple cytokines, and CD8αβ+ T cells and NK cells expressing cytotoxic effectors in airways. We also detected higher levels of mycobacteria-specific IgG and IgM in the airways of i.v. BCG-vaccinated MCM. Although i.v. BCG vaccination resulted in an influx of tissue-resident memory T cells in lungs of MCM with controlled SIV replication, MCM with high plasma SIV RNA (>105 copies/ml) typically displayed reduced T cell responses, suggesting that uncontrolled SIV or HIV replication would have a detrimental effect on i.v. BCG-induced protection against M. tuberculosis.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289201","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

Type I IFN Induces TCR-dependent and -independent Antimicrobial Responses in γδ Intraepithelial Lymphocytes. I 型 IFN 在γδ上皮内淋巴细胞中诱导依赖和不依赖 TCR 的抗微生物反应。

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-09-23 DOI: 10.4049/jimmunol.2400138

Matthew A Fischer, Luo Jia, Karen L Edelblum

{"title":"Type I IFN Induces TCR-dependent and -independent Antimicrobial Responses in γδ Intraepithelial Lymphocytes.","authors":"Matthew A Fischer, Luo Jia, Karen L Edelblum","doi":"10.4049/jimmunol.2400138","DOIUrl":"10.4049/jimmunol.2400138","url":null,"abstract":"Intraepithelial lymphocytes (IELs) expressing the TCRγδ survey the intestinal epithelium to limit the invasion of microbial pathogens. The production of type I IFN is a central component of an antiviral immune response, yet how these proinflammatory cytokines contribute to γδ IEL effector function remains unclear. Based on the unique activation status of IELs and their ability to bridge innate and adaptive immunity, we investigated the extent to which type I IFN signaling modulates γδ IEL function. Using an ex vivo culture model, we find that type I IFN alone is unable to drive IFN-γ production, yet low-level TCR activation synergizes with type I IFN to induce IFN-γ production in murine γδ IELs. Further investigation into the underlying molecular mechanisms of costimulation revealed that TCRγδ-mediated activation of NFAT and JNK is required for type I IFN to promote IFN-γ expression in a STAT4-dependent manner. Whereas type I IFN rapidly upregulates antiviral gene expression independent of a basal TCRγδ signal, neither tonic TCR triggering nor the presence of a TCR agonist was sufficient to elicit type I IFN-induced IFN-γ production in vivo. However, bypassing proximal TCR signaling events synergized with IFNAR/STAT4 activation to induce γδ IEL IFN-γ production. These findings indicate that γδ IELs contribute to host defense in response to type I IFN by mounting a rapid antimicrobial response independent of TCRγδ signaling, and may produce IFN-γ in a TCR-dependent manner under permissive conditions.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289205","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}

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