ImmunoHorizons最新文献_第10页

Strong Basal/Tonic TCR Signals Are Associated with Negative Regulation of Naive CD4+ T Cells 强基础/强直TCR信号与初始CD4+ T细胞负调控相关

ImmunoHorizons Pub Date : 2022-04-20 DOI: 10.1101/2022.04.20.488956

Wendy M. Zinzow-Kramer, E. Kolawole, J. Eggert, B. Evavold, Christopher D. Scharer, Byron B. Au-Yeung

{"title":"Strong Basal/Tonic TCR Signals Are Associated with Negative Regulation of Naive CD4+ T Cells","authors":"Wendy M. Zinzow-Kramer, E. Kolawole, J. Eggert, B. Evavold, Christopher D. Scharer, Byron B. Au-Yeung","doi":"10.1101/2022.04.20.488956","DOIUrl":"https://doi.org/10.1101/2022.04.20.488956","url":null,"abstract":"T cells experience varying intensities of tonic or basal TCR signaling in response to self-peptides presented by MHC (self-pMHC) in vivo. We analyzed four subpopulations of mouse naive CD4+ cells that express different levels of Nur77-GFP and Ly6C, surrogate markers that positively and inversely correlate with the strength of tonic TCR signaling, respectively. Adoptive transfer studies suggest that relatively weak or strong Nur77-GFP intensity in thymocytes tends to be maintained in mature T cells. Two-dimensional affinity measurements were lowest for Nur77-GFPloLy6C+ cells and highest for Nur77-GFPhiLy6C− cells, highlighting a positive correlation between apparent TCR affinity and tonic TCR signal strength. Despite experiencing the strongest tonic TCR signaling, Nur77-GFPhiLy6C− cells were least responsive to multiple concentrations of a cognate or suboptimal pMHC. Gene expression analyses suggest that Nur77-GFPhiLy6C− cells induce a gene expression program that has similarities with that of acutely stimulated T cells. However, strong tonic TCR signaling also correlates with increased expression of genes with inhibitory functions, including coinhibitory receptors. Similarly, assay for transposase-accessible chromatin with sequencing analyses suggested that increased tonic TCR signal strength correlated with increased chromatin accessibility associated with genes that have positive and inhibitory roles in T cell activation. Strikingly, Nur77-GFPhiLy6C− cells exhibited differential accessibility within regions of Cd200r1 and Tox that were similar in location to differentially accessible regions previously identified in exhausted CD8+ T cells. We propose that constitutive strong tonic TCR signaling triggers adaptations detectable at both the transcriptional and epigenetic levels, ultimately contributing to the tuning of T cell responsiveness.","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46161641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

The Statue of Publication Liberty 出版自由女神像

ImmunoHorizons Pub Date : 2022-04-01 DOI: 10.4049/immunohorizons.2200024

Mark Kaplan

引用次数: 0

Prophylactic Vaccine Targeting TLR3 on Dendritic Cells Ameliorates Eosinophilic Pneumonia in a Mouse SARS-CoV Infection Model 树突状细胞靶向TLR3的预防性疫苗改善小鼠SARS-CoV感染模型中的嗜酸性肺炎

ImmunoHorizons Pub Date : 2022-04-01 DOI: 10.4049/immunohorizons.2200020

N. Iwata-Yoshikawa, N. Nagata, Hiromi Takaki, M. Matsumoto, Tadaki Suzuki, H. Hasegawa, T. Seya

{"title":"Prophylactic Vaccine Targeting TLR3 on Dendritic Cells Ameliorates Eosinophilic Pneumonia in a Mouse SARS-CoV Infection Model","authors":"N. Iwata-Yoshikawa, N. Nagata, Hiromi Takaki, M. Matsumoto, Tadaki Suzuki, H. Hasegawa, T. Seya","doi":"10.4049/immunohorizons.2200020","DOIUrl":"https://doi.org/10.4049/immunohorizons.2200020","url":null,"abstract":"Putative subcomponent vaccines of severe acute respiratory syndrome coronavirus spike protein and ARNAX (TLR3-specific adjuvant for priming dendritic cells) were examined and compared with spike protein + Alum in a mouse BALB/c model. Survival, body weight, virus-neutralizing Ab titer in the blood, and viral titer in the lung were evaluated for prognosis markers. The infiltration degrees of eosinophils in the lung were histopathologically monitored at 10 d postinfection. The results were: (1) adjuvant was essential in vaccines to achieve a complete recovery from infection, (2) ARNAX displayed optimal body weight recovery compared with Alum, (3) ARNAX was optimal for the amelioration of eosinophilic pneumonia, and (4) the eosinophil infiltration score was not associated with the neutralizing Ab titer in the blood or viral titer in the lung. Although the pathological link between the TLR3 vaccine and lung eosinophil infiltration remains unclear, severe acute respiratory syndrome–mediated eosinophilic pneumonia can be blocked by the prior induction of dendritic cell priming by ARNAX.","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41979538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

MAdCAM-1 Costimulates T Cells through Integrin α4β7 to Cause Gene Expression Events Resembling Costimulation through CD28 MAdCAM-1通过整合素α4β7共刺激T细胞，引起类似CD28共刺激的基因表达事件

ImmunoHorizons Pub Date : 2022-03-01 DOI: 10.4049/immunohorizons.2200009

H. DeBerg, A. Konecny, D. Shows, J. Lord

{"title":"MAdCAM-1 Costimulates T Cells through Integrin α4β7 to Cause Gene Expression Events Resembling Costimulation through CD28","authors":"H. DeBerg, A. Konecny, D. Shows, J. Lord","doi":"10.4049/immunohorizons.2200009","DOIUrl":"https://doi.org/10.4049/immunohorizons.2200009","url":null,"abstract":"Successful treatment of inflammatory bowel disease (IBD) with the anti-integrin α4β7 mAb vedolizumab suggests that interaction of this integrin with addressin mucosal addressin cell adhesion molecule-1 (MAdCAM-1) is central to IBD pathogenesis. Although this was presumed to be due to an inhibition of lymphocyte trafficking to the gut, as has been observed in animal models, we report no depletion of CD4 T cells from the colonic mucosa as a consequence of vedolizumab treatment in humans, regardless of efficacy. Likewise, no upregulation of alternative trafficking mechanisms was observed as a consequence of therapy to suggest that this homeostasis is maintained in patients by a mechanistic escape from inhibition. Instead, we explore a role for MAdCAM–integrin interaction as a gut-specific costimulatory signal, demonstrating that it can replace CD28 ligation to activate human T cells in vitro. This activation through integrin α4β7 is mediated through the gut-restricted molecule MAdCAM-1, and it cannot be replicated by matrix molecules or proteins that bind other integrins. A detailed analysis of mRNA expression by human T cell subsets following suboptimal TCR stimulation in the presence or absence of CD28 versus MAdCAM-1 costimulation reveals marked similarity in the effect that these two signals have upon T cells, with temporal or quantitative differences detected in the expression of cytokines associated with Th17 cells or pyogenic inflammation. Thus, we describe an alternative costimulatory pathway for T cells in the intestine, through ligation of integrin α4β7 by MAdCAM-1, which may explain the therapeutic efficacy of vedolizumab and have implications concerning the treatment of IBD.","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45968870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

NLRC4 Deficiency Leads to Enhanced Phosphorylation of MLKL and Necroptosis NLRC4缺失导致MLKL磷酸化增强和坏死性坏死

ImmunoHorizons Pub Date : 2022-03-01 DOI: 10.4049/immunohorizons.2100118

Balamurugan Sundaram, Rajendra Karki, T. Kanneganti

{"title":"NLRC4 Deficiency Leads to Enhanced Phosphorylation of MLKL and Necroptosis","authors":"Balamurugan Sundaram, Rajendra Karki, T. Kanneganti","doi":"10.4049/immunohorizons.2100118","DOIUrl":"https://doi.org/10.4049/immunohorizons.2100118","url":null,"abstract":"Hosts rely on the innate immune system to clear pathogens in response to infection. Pathogen-associated molecular patterns bind to innate immune receptors and engage activation of downstream signaling to initiate a host immune response to fight infection. A key component of this innate response is programmed cell death. Recent work has highlighted significant cross-talk and functional redundancy between cell death pathways, leading to the discovery of PANoptosis, an inflammatory programmed cell death pathway dependent on PANoptosomes, which are innate immune danger-sensing complexes that activate inflammatory cell death and contain caspases with or without inflammasome components and receptor interacting protein homotypic interaction motif–containing proteins. Although PANoptosis has been characterized in response to a growing number of pathogens, inflammatory diseases, and cancer, its role and the functional consequences of PANoptotic component modulation during NLR family CARD domain-containing protein 4 (NLRC4) activation by Pseudomonas aeruginosa infection remain unknown. In this study, we show that P. aeruginosa can induce PANoptosis in mouse bone marrow–derived macrophages (BMDMs). Only the combined deletion of caspase-1, -11, -8, and RIPK3 protected mouse BMDMs from cell death. Moreover, we showed that PANoptotic components act in a compensatory manner; in the absence of NAIP5 and NLRC4 during P. aeruginosa challenge, activation of caspase-1, -3, -7, and -8 was reduced, whereas alternative cell death molecules such as RIPK1 and MLKL were activated in mouse BMDMs. Taken together, these data highlight the extensive cross-talk between cell death signaling molecules and showcase the plasticity of the system.","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44566646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Long-Lasting Virus-Specific T Cell Response with Divergent Features in Self-Resolved and Chronic Hepatitis C Virus Patients 35 Years Postinfection 慢性丙型肝炎患者感染35年后具有不同特征的持久病毒特异性T细胞反应

ImmunoHorizons Pub Date : 2022-03-01 DOI: 10.4049/immunohorizons.2200008

Wei Ji, Min Zhao, Jikun Zhou, Huanwei Zheng, Naizhe Li, B. Han, Wen-jiao Yin, Shengli Bi, G. Gao, Yong Zhang, William J. Liu

{"title":"Long-Lasting Virus-Specific T Cell Response with Divergent Features in Self-Resolved and Chronic Hepatitis C Virus Patients 35 Years Postinfection","authors":"Wei Ji, Min Zhao, Jikun Zhou, Huanwei Zheng, Naizhe Li, B. Han, Wen-jiao Yin, Shengli Bi, G. Gao, Yong Zhang, William J. Liu","doi":"10.4049/immunohorizons.2200008","DOIUrl":"https://doi.org/10.4049/immunohorizons.2200008","url":null,"abstract":"Although recognized as a curable disease, the persistence of hepatitis C virus (HCV) in chronically infected patients remains a great burden for public health. T cell immune responses serve a key role in anti-HCV infection; however, the features of T cell immunity in patients after a long-term infection are not well explored. We recruited a special cohort of patients with similar genetic background and natural developing progression of disease who were infected with HCV through blood donation 35 y ago. We found that self-resolved individuals had higher levels of cytokine-secreting T cells than individuals with chronic infections, indicating HCV-specific T cell immunity could be sustained for >35 y. Meanwhile, virus-specific CD8+ T cells in chronic patients were characterized by programmed cell death-1high, TIM-3high expression, which was related to liver injury characterized by aspartate transaminase/alanine aminotransferase levels and morphopathological changes. Unexpectedly, the expression of Lymphocyte-activation gene 3 on CD8+ T cells was lower in chronic patients and negatively correlated with alanine aminotransferase/aspartate transaminase. Our findings provided new insights into HCV-specific T cell responses and may shed light on a way to figure out novel effector targets and explore a way to reverse chronic infections.","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46670216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Contribution of Protein Kinase D1 on Acute Pulmonary Inflammation and Hypersensitivity Pneumonitis Induced by Saccharopolyspora rectivirgula 蛋白激酶D1在糖多孢子虫致急性肺部炎症和超敏性肺炎中的作用

ImmunoHorizons Pub Date : 2022-03-01 DOI: 10.4049/immunohorizons.2200017

T. Yoon, E. Fitzpatrick, J. Snyder, Sangmin Lee, Young-In Kim, Chidi Zacheaus, A. Yi

{"title":"Contribution of Protein Kinase D1 on Acute Pulmonary Inflammation and Hypersensitivity Pneumonitis Induced by Saccharopolyspora rectivirgula","authors":"T. Yoon, E. Fitzpatrick, J. Snyder, Sangmin Lee, Young-In Kim, Chidi Zacheaus, A. Yi","doi":"10.4049/immunohorizons.2200017","DOIUrl":"https://doi.org/10.4049/immunohorizons.2200017","url":null,"abstract":"Protein kinase D1 (PKD1), a ubiquitously expressed serine/threonine kinase, regulates diverse cellular processes such as oxidative stress, gene expression, cell survival, vesicle trafficking, Ag receptor signaling, and pattern recognition receptor signaling. We found previously that exposure to hypersensitivity pneumonitis (HP) inciting Ag Saccharopolyspora rectivirgula leads to the activation of PKD1 in a MyD88-dependent manner in various types of murine cells in vitro and in the mouse lung in vivo. However, it is currently unknown whether PKD1 plays a role in the S. rectivirgula–induced HP. In this study, we investigated contributions of PKD1 on the S. rectivirgula–induced HP using conditional PKD1-insufficient mice. Compared to control PKD1-sufficient mice, PKD1-insufficient mice showed substantially suppressed activation of MAPKs and NF-κB, expression of cytokines and chemokines, and neutrophilic alveolitis after single intranasal exposure to S. rectivirgula. The significantly reduced levels of alveolitis, MHC class II surface expression on neutrophils and macrophages, and IL-17A and CXCL9 expression in lung tissue were observed in the PKD1-insufficient mice repeatedly exposed to S. rectivirgula for 5 wk. PKD1-insuficient mice exposed to S. rectivirgula for 5 wk also showed reduced granuloma formation. Our results demonstrate that PKD1 plays an essential role in the initial proinflammatory responses and neutrophil influx in the lung after exposure to S. rectivirgula and substantially contribute to the development of HP caused by repeated exposure to S. rectivirgula. Our findings suggest that PKD1 can be an attractive new molecular target for therapy of S. rectivirgula–induced HP.","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41405944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

No Major Impact of Two Homologous Proteins Ly6C1 and Ly6C2 on Immune Homeostasis 两种同源蛋白Ly6C1和Ly6C2对免疫稳态无重大影响

ImmunoHorizons Pub Date : 2022-03-01 DOI: 10.4049/immunohorizons.2100114

J. Morimoto, Minoru Matsumoto, Ryuichiro Miyazawa, T. Oya, Koichi Tsuneyama, M. Matsumoto

{"title":"No Major Impact of Two Homologous Proteins Ly6C1 and Ly6C2 on Immune Homeostasis","authors":"J. Morimoto, Minoru Matsumoto, Ryuichiro Miyazawa, T. Oya, Koichi Tsuneyama, M. Matsumoto","doi":"10.4049/immunohorizons.2100114","DOIUrl":"https://doi.org/10.4049/immunohorizons.2100114","url":null,"abstract":"Ly6C comprises two homologous components of Ly6C1 and Ly6C2, and the expression of either of the Ly6C molecules defines unique functional subsets of monocytes. Ly6C is also expressed by other immune cell types, including Aire-expressing medullary thymic epithelial cells. Because the role of Ly6C expression in determining the functional subsets remains unclear, we generated mice deficient for both Ly6C1 and Ly6C2 with CRISPR-Cas9–mediated deletion. Mice deficient for Ly6C1/Ly6C2 showed no major alterations in the subsets and function of monocyte and other immune cells, including the cells involved in the dextran sulfate sodium salt–induced colitis model. By generating the mice deficient for Ly6C1 alone, we have also investigated the expression pattern of Ly6C1 and Ly6C2 in immune cells. Except for medullary thymic epithelial cells and CD4 single-positive T cells, immune cells predominantly expressed Ly6C2. Thus, despite the importance as a marker with a unique differential expression pattern, the Ly6C molecules have no major impact on determining the functional subsets and maintaining immune homeostasis.","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42092391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Bat Red Blood Cells Express Nucleic Acid–Sensing Receptors and Bind RNA and DNA 蝙蝠红细胞表达核酸感应受体并结合RNA和DNA

ImmunoHorizons Pub Date : 2022-01-14 DOI: 10.1101/2022.01.13.476238

L. M. Lam, J. Dobkin, K. Eckart, Ian Gereg, A. DiSalvo, Amber Nolder, Eman Anis, J. Ellis, Greg Turner, N. Mangalmurti

引用次数: 0

The E26 Transformation-Specific Family Transcription Factor Spi-C Is Dynamically Regulated by External Signals in B Cells. E26转化特异性家族转录因子Spi-C在B细胞中受外部信号的动态调节

ImmunoHorizons Pub Date : 2022-01-01 DOI: 10.4049/immunohorizons.2100111

Hannah L Raczkowski, Li S Xu, Wei Cen Wang, Rodney P Dekoter

引用次数: 0