The Journal of Immunology Author Choice最新文献_第2页

Primary EBV Infection Induces an Acute Wave of Activated Antigen-Specific Cytotoxic CD4+ T Cells 原发性EBV感染诱导急性激活抗原特异性细胞毒性CD4+ T细胞波

The Journal of Immunology Author Choice Pub Date : 2019-07-15 DOI: 10.4049/jimmunol.1900377

Benjamin J Meckiff, K. Ladell, J. McLaren, Gordon B Ryan, A. Leese, E. James, D. Price, H. Long

{"title":"Primary EBV Infection Induces an Acute Wave of Activated Antigen-Specific Cytotoxic CD4+ T Cells","authors":"Benjamin J Meckiff, K. Ladell, J. McLaren, Gordon B Ryan, A. Leese, E. James, D. Price, H. Long","doi":"10.4049/jimmunol.1900377","DOIUrl":"https://doi.org/10.4049/jimmunol.1900377","url":null,"abstract":"Key Points Primary EBV infection drives highly cytotoxic virus-specific CD4+ T cell responses. EBV-specific memory CD4+ T cells are polyfunctional but lack cytotoxic activity. Acute EBV-specific CD4-CTLs differ transcriptionally from classical memory CD4-CTLs. CD4+ T cells are essential for immune protection against viruses, yet their multiple roles remain ill-defined at the single-cell level in humans. Using HLA class II tetramers, we studied the functional properties and clonotypic architecture of EBV-specific CD4+ T cells in patients with infectious mononucleosis, a symptomatic manifestation of primary EBV infection, and in long-term healthy carriers of EBV. We found that primary infection elicited oligoclonal expansions of TH1-like EBV-specific CD4+ T cells armed with cytotoxic proteins that responded immediately ex vivo to challenge with EBV-infected B cells. Importantly, these acutely generated cytotoxic CD4+ T cells were highly activated and transcriptionally distinct from classically described cytotoxic CD4+ memory T cells that accumulate during other persistent viral infections, including CMV and HIV. In contrast, EBV-specific memory CD4+ T cells displayed increased cytokine polyfunctionality but lacked cytotoxic activity. These findings suggested an important effector role for acutely generated cytotoxic CD4+ T cells that could potentially be harnessed to improve the efficacy of vaccines against EBV.","PeriodicalId":310446,"journal":{"name":"The Journal of Immunology Author Choice","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129204089","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: 35

Inflammasome-Independent Role for NLRP3 in Controlling Innate Antihelminth Immunity and Tissue Repair in the Lung NLRP3在控制肺部先天抗蠕虫免疫和组织修复中的非炎性体作用

The Journal of Immunology Author Choice Pub Date : 2019-04-13 DOI: 10.4049/jimmunol.1900640

Alistair L. Chenery, R. Alhallaf, Z. Agha, J. Ajendra, James E. Parkinson, Martha M. Cooper, B. Chan, R. Eichenberger, L. Dent, A. Robertson, A. Kupz, D. Brough, A. Loukas, T. Sutherland, J. Allen, P. Giacomin

{"title":"Inflammasome-Independent Role for NLRP3 in Controlling Innate Antihelminth Immunity and Tissue Repair in the Lung","authors":"Alistair L. Chenery, R. Alhallaf, Z. Agha, J. Ajendra, James E. Parkinson, Martha M. Cooper, B. Chan, R. Eichenberger, L. Dent, A. Robertson, A. Kupz, D. Brough, A. Loukas, T. Sutherland, J. Allen, P. Giacomin","doi":"10.4049/jimmunol.1900640","DOIUrl":"https://doi.org/10.4049/jimmunol.1900640","url":null,"abstract":"Key Points Nlrp3−/− mice have enhanced early antihelminth immunity in the lung. Type 2 immunity and repair responses are dysregulated in Nlrp3−/− mice. NLRP3 plays an inflammasome-independent role during Nippostrongylus infection. Alternatively activated macrophages are essential effector cells during type 2 immunity and tissue repair following helminth infections. We previously showed that Ym1, an alternative activation marker, can drive innate IL-1R–dependent neutrophil recruitment during infection with the lung-migrating nematode, Nippostrongylus brasiliensis, suggesting a potential role for the inflammasome in the IL-1–mediated innate response to infection. Although inflammasome proteins such as NLRP3 have important proinflammatory functions in macrophages, their role during type 2 responses and repair are less defined. We therefore infected Nlrp3−/− mice with N. brasiliensis. Unexpectedly, compared with wild-type (WT) mice, infected Nlrp3−/− mice had increased neutrophilia and eosinophilia, correlating with enhanced worm killing but at the expense of increased tissue damage and delayed lung repair. Transcriptional profiling showed that infected Nlrp3−/− mice exhibited elevated type 2 gene expression compared with WT mice. Notably, inflammasome activation was not evident early postinfection with N. brasiliensis, and in contrast to Nlrp3−/− mice, antihelminth responses were unaffected in caspase-1/11–deficient or WT mice treated with the NLRP3-specific inhibitor MCC950. Together these data suggest that NLRP3 has a role in constraining lung neutrophilia, helminth killing, and type 2 immune responses in an inflammasome-independent manner.","PeriodicalId":310446,"journal":{"name":"The Journal of Immunology Author Choice","volume":"133 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127308618","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: 19

Monocyte Subsets Coregulate Inflammatory Responses by Integrated Signaling through TNF and IL-6 at the Endothelial Cell Interface 单核细胞亚群在内皮细胞界面通过TNF和IL-6的综合信号共同调节炎症反应

The Journal of Immunology Author Choice Pub Date : 2017-02-13 DOI: 10.4049/jimmunol.1601281

M. Chimen, C. Yates, H. McGettrick, Lewis S C Ward, M. Harrison, B. Apta, Lea Dib, B. Imhof, P. Harrison, G. Nash, G. Rainger

{"title":"Monocyte Subsets Coregulate Inflammatory Responses by Integrated Signaling through TNF and IL-6 at the Endothelial Cell Interface","authors":"M. Chimen, C. Yates, H. McGettrick, Lewis S C Ward, M. Harrison, B. Apta, Lea Dib, B. Imhof, P. Harrison, G. Nash, G. Rainger","doi":"10.4049/jimmunol.1601281","DOIUrl":"https://doi.org/10.4049/jimmunol.1601281","url":null,"abstract":"Two major monocyte subsets, CD14+CD16− (classical) and CD14+/dimCD16+ (nonclassical/intermediate), have been described. Each has different functions ascribed in its interactions with vascular endothelial cells (EC), including migration and promoting inflammation. Although monocyte subpopulations have been studied in isolated systems, their influence on EC and on the course of inflammation has been ignored. In this study, using unstimulated or cytokine-activated EC, we observed significant differences in the recruitment, migration, and reverse migration of human monocyte subsets. Associated with this, and based on their patterns of cytokine secretion, there was a difference in their capacity to activate EC and support the secondary recruitment of flowing neutrophils. High levels of TNF were detected in cocultures with nonclassical/intermediate monocytes, the blockade of which significantly reduced neutrophil recruitment. In contrast, classical monocytes secreted high levels of IL-6, the blockade of which resulted in increased neutrophil recruitment. When cocultures contained both monocyte subsets, or when conditioned supernatant from classical monocytes cocultures (IL-6hi) was added to nonclassical/intermediate monocyte cocultures (TNFhi), the activating effects of TNF were dramatically reduced, implying that when present, the anti-inflammatory activities of IL-6 were dominant over the proinflammatory activities of TNF. These changes in neutrophil recruitment could be explained by regulation of E-selectin on the cocultured EC. This study suggests that recruited human monocyte subsets trigger a regulatory pathway of cytokine-mediated signaling at the EC interface, and we propose that this is a mechanism for limiting the phlogistic activity of newly recruited monocytes.","PeriodicalId":310446,"journal":{"name":"The Journal of Immunology Author Choice","volume":"17 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2017-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131604614","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: 76

A B Cell Epitope Peptide Derived from the Major Grass Pollen Allergen Phl p 1 Boosts Allergen-Specific Secondary Antibody Responses without Allergen-Specific T Cell Help 草花粉过敏原php1衍生的B细胞表位肽在没有过敏原特异性T细胞帮助的情况下增强过敏原特异性二抗反应

The Journal of Immunology Author Choice Pub Date : 2017-01-16 DOI: 10.4049/jimmunol.1501741

Meena Narayanan, Raphaela Freidl, M. Focke‐Tejkl, U. Baranyi, T. Wekerle, R. Valenta, B. Linhart

{"title":"A B Cell Epitope Peptide Derived from the Major Grass Pollen Allergen Phl p 1 Boosts Allergen-Specific Secondary Antibody Responses without Allergen-Specific T Cell Help","authors":"Meena Narayanan, Raphaela Freidl, M. Focke‐Tejkl, U. Baranyi, T. Wekerle, R. Valenta, B. Linhart","doi":"10.4049/jimmunol.1501741","DOIUrl":"https://doi.org/10.4049/jimmunol.1501741","url":null,"abstract":"More than 40% of allergic patients suffer from grass pollen allergy. Phl p 1, the major timothy grass pollen allergen, belongs to the cross-reactive group 1 grass pollen allergens that are thought to initiate allergic sensitization to grass pollen. Repeated allergen encounter boosts allergen-specific IgE production and enhances clinical sensitivity in patients. To investigate immunological mechanisms underlying the boosting of allergen-specific secondary IgE Ab responses and the allergen epitopes involved, a murine model for Phl p 1 was established. A B cell epitope–derived peptide of Phl p 1 devoid of allergen-specific T cell epitopes, as recognized by BALB/c mice, was fused to an allergen-unrelated carrier in the form of a recombinant fusion protein and used for sensitization. This fusion protein allowed the induction of allergen-specific IgE Ab responses without allergen-specific T cell help. Allergen-specific Ab responses were subsequently boosted with molecules containing the B cell epitope–derived peptide without carrier or linked to other allergen-unrelated carriers. Oligomeric peptide bound to a carrier different from that which had been used for sensitization boosted allergen-specific secondary IgE responses without a detectable allergen-specific T cell response. Our results indicate that allergen-specific secondary IgE Ab responses can be boosted by repetitive B cell epitopes without allergen-specific T cell help by cross-linking of the B cell epitope receptor. This finding has important implications for the design of new allergy vaccines.","PeriodicalId":310446,"journal":{"name":"The Journal of Immunology Author Choice","volume":"25 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2017-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115023059","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: 11

The Threshold of Protection from Liver-Stage Malaria Relies on a Fine Balance between the Number of Infected Hepatocytes and Effector CD8+ T Cells Present in the Liver 肝期疟疾的保护阈值依赖于受感染肝细胞和肝脏中CD8+效应T细胞数量之间的微妙平衡

The Journal of Immunology Author Choice Pub Date : 2017-01-13 DOI: 10.4049/jimmunol.1601209

Alexandra J. Spencer, Rhea J. Longley, Anita Gola, M. Ulaszewska, T. Lambe, A. Hill

{"title":"The Threshold of Protection from Liver-Stage Malaria Relies on a Fine Balance between the Number of Infected Hepatocytes and Effector CD8+ T Cells Present in the Liver","authors":"Alexandra J. Spencer, Rhea J. Longley, Anita Gola, M. Ulaszewska, T. Lambe, A. Hill","doi":"10.4049/jimmunol.1601209","DOIUrl":"https://doi.org/10.4049/jimmunol.1601209","url":null,"abstract":"Since the demonstration of sterile protection afforded by injection of irradiated sporozoites, CD8+ T cells have been shown to play a significant role in protection from liver-stage malaria. This is, however, dependent on the presence of an extremely high number of circulating effector cells, thought to be necessary to scan, locate, and kill infected hepatocytes in the short time that parasites are present in the liver. We used an adoptive transfer model to elucidate the kinetics of the effector CD8+ T cell response in the liver following Plasmodium berghei sporozoite challenge. Although effector CD8+ T cells require <24 h to find, locate, and kill infected hepatocytes, active migration of Ag-specific CD8+ T cells into the liver was not observed during the 2-d liver stage of infection, as divided cells were only detected from day 3 postchallenge. However, the percentage of donor cells recruited into division was shown to indicate the level of Ag presentation from infected hepatocytes. By titrating the number of transferred Ag-specific effector CD8+ T cells and sporozoites, we demonstrate that achieving protection toward liver-stage malaria is reliant on CD8+ T cells being able to locate infected hepatocytes, resulting in a protection threshold dependent on a fine balance between the number of infected hepatocytes and CD8+ T cells present in the liver. With such a fine balance determining protection, achieving a high number of CD8+ T cells will be critical to the success of a cell-mediated vaccine against liver-stage malaria.","PeriodicalId":310446,"journal":{"name":"The Journal of Immunology Author Choice","volume":"65 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2017-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126505173","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: 17

T Cells Infiltrating Diseased Liver Express Ligands for the NKG2D Stress Surveillance System 浸润病变肝脏的T细胞表达NKG2D应激监测系统的配体

The Journal of Immunology Author Choice Pub Date : 2016-12-28 DOI: 10.4049/jimmunol.1601313

Wei‐Chen Huang, N. Easom, Xin-Zi Tang, U. Gill, Harsimran D. Singh, F. Robertson, Chiwen Chang, J. Trowsdale, B. Davidson, W. Rosenberg, G. Fusai, A. Toubert, P. Kennedy, D. Peppa, M. Maini

{"title":"T Cells Infiltrating Diseased Liver Express Ligands for the NKG2D Stress Surveillance System","authors":"Wei‐Chen Huang, N. Easom, Xin-Zi Tang, U. Gill, Harsimran D. Singh, F. Robertson, Chiwen Chang, J. Trowsdale, B. Davidson, W. Rosenberg, G. Fusai, A. Toubert, P. Kennedy, D. Peppa, M. Maini","doi":"10.4049/jimmunol.1601313","DOIUrl":"https://doi.org/10.4049/jimmunol.1601313","url":null,"abstract":"NK cells, which are highly enriched in the liver, are potent regulators of antiviral T cells and immunopathology in persistent viral infection. We investigated the role of the NKG2D axis in T cell/NK cell interactions in hepatitis B. Activated and hepatitis B virus (HBV)–specific T cells, particularly the CD4 fraction, expressed NKG2D ligands (NKG2DL), which were not found on T cells from healthy controls (p < 0.001). NKG2DL-expressing T cells were strikingly enriched within HBV-infected livers compared with the periphery or to healthy livers (p < 0.001). NKG2D+NK cells were also increased and preferentially activated in the HBV-infected liver (p < 0.001), in direct proportion to the percentage of MICA/B-expressing CD4 T cells colocated within freshly isolated liver tissue (p < 0.001). This suggests that NKG2DL induced on T cells within a diseased organ can calibrate NKG2D-dependent activation of local NK cells; furthermore, NKG2D blockade could rescue HBV-specific and MICA/B-expressing T cells from HBV-infected livers. To our knowledge, this is the first ex vivo demonstration that non-virally infected human T cells can express NKG2DL, with implications for stress surveillance by the large number of NKG2D-expressing NK cells sequestered in the liver.","PeriodicalId":310446,"journal":{"name":"The Journal of Immunology Author Choice","volume":"37 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126113892","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: 40

Type I IFN Inhibits Alternative Macrophage Activation during Mycobacterium tuberculosis Infection and Leads to Enhanced Protection in the Absence of IFN-γ Signaling I型IFN抑制结核分枝杆菌感染期间巨噬细胞的选择性激活，并在缺乏IFN-γ信号传导的情况下增强保护作用

The Journal of Immunology Author Choice Pub Date : 2016-11-14 DOI: 10.4049/jimmunol.1600584

Lúcia Moreira-Teixeira, J. Sousa, Finlay W Mcnab, E. Torrado, Filipa Cardoso, Henrique Machado, Flávia Castro, Vânia Cardoso, J. Gaifem, Xuemei Wu, R. Appelberg, A. Castro, A. O’Garra, M. Saraiva

{"title":"Type I IFN Inhibits Alternative Macrophage Activation during Mycobacterium tuberculosis Infection and Leads to Enhanced Protection in the Absence of IFN-γ Signaling","authors":"Lúcia Moreira-Teixeira, J. Sousa, Finlay W Mcnab, E. Torrado, Filipa Cardoso, Henrique Machado, Flávia Castro, Vânia Cardoso, J. Gaifem, Xuemei Wu, R. Appelberg, A. Castro, A. O’Garra, M. Saraiva","doi":"10.4049/jimmunol.1600584","DOIUrl":"https://doi.org/10.4049/jimmunol.1600584","url":null,"abstract":"Tuberculosis causes ∼1.5 million deaths every year, thus remaining a leading cause of death from infectious diseases in the world. A growing body of evidence demonstrates that type I IFN plays a detrimental role in tuberculosis pathogenesis, likely by interfering with IFN-γ–dependent immunity. In this article, we reveal a novel mechanism by which type I IFN may confer protection against Mycobacterium tuberculosis infection in the absence of IFN-γ signaling. We show that production of type I IFN by M. tuberculosis–infected macrophages induced NO synthase 2 and inhibited arginase 1 gene expression. In vivo, absence of both type I and type II IFN receptors led to strikingly increased levels of arginase 1 gene expression and protein activity in infected lungs, characteristic of alternatively activated macrophages. This correlated with increased lung bacterial burden and pathology and decreased survival compared with mice deficient in either receptor. Increased expression of other genes associated with alternatively activated macrophages, as well as increased expression of Th2-associated cytokines and decreased TNF expression, were also observed. Thus, in the absence of IFN-γ signaling, type I IFN suppressed the switching of macrophages from a more protective classically activated phenotype to a more permissive alternatively activated phenotype. Together, our data support a model in which suppression of alternative macrophage activation by type I IFN during M. tuberculosis infection, in the absence of IFN-γ signaling, contributes to host protection.","PeriodicalId":310446,"journal":{"name":"The Journal of Immunology Author Choice","volume":"126 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128073445","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: 75

Suppression of IRAK1 or IRAK4 Catalytic Activity, but Not Type 1 IFN Signaling, Prevents Lupus Nephritis in Mice Expressing a Ubiquitin Binding–Defective Mutant of ABIN1 抑制IRAK1或IRAK4的催化活性，而不是1型IFN信号，可以预防表达ABIN1泛素结合缺陷突变体的小鼠狼疮肾炎

The Journal of Immunology Author Choice Pub Date : 2016-11-02 DOI: 10.4049/jimmunol.1600788

S. Nanda, M. López-Peláez, J. Arthur, F. Marchesi, P. Cohen

{"title":"Suppression of IRAK1 or IRAK4 Catalytic Activity, but Not Type 1 IFN Signaling, Prevents Lupus Nephritis in Mice Expressing a Ubiquitin Binding–Defective Mutant of ABIN1","authors":"S. Nanda, M. López-Peláez, J. Arthur, F. Marchesi, P. Cohen","doi":"10.4049/jimmunol.1600788","DOIUrl":"https://doi.org/10.4049/jimmunol.1600788","url":null,"abstract":"Polymorphisms in the TNIP1 gene encoding A20-binding inhibitor of NF-κB1 (ABIN1) predispose to lupus and other autoimmune diseases in at least eight human populations. We found previously that knock-in mice expressing a ubiquitin-binding–defective mutant of ABIN1 (ABIN1[D485N]) develop autoimmunity as they age and succumb to a disease resembling lupus nephritis in humans. In this article, we report that Flt3-derived dendritic cells from these mice overproduced type 1 IFNs upon stimulation with ligands that activate TLR7 or TLR9. However, crossing ABIN1[D485N] mice to IFNAR1-knockout mice that do not express the α-subunit of the type 1 IFNR did not prevent splenomegaly, the appearance of high serum levels of autoantibodies and other Igs, or liver inflammation and only reduced kidney inflammation modestly. In contrast, crossing ABIN1[D485N] mice to knock-in mice expressing catalytically inactive mutants of IRAK1 or IRAK4 prevented splenomegaly, autoimmunity, and liver and kidney inflammation. Our results support the notion that IRAK1 and/or IRAK4 are attractive targets for the development of drugs to prevent, and perhaps treat, lupus nephritis and other autoinflammatory diseases caused by the decreased ability of ABIN1 or other proteins to restrict the strength of MyD88 signaling.","PeriodicalId":310446,"journal":{"name":"The Journal of Immunology Author Choice","volume":"71 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123806211","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: 49

PTPN22 Is a Critical Regulator of Fcγ Receptor–Mediated Neutrophil Activation PTPN22是Fcγ受体介导的中性粒细胞活化的关键调节因子

The Journal of Immunology Author Choice Pub Date : 2016-11-02 DOI: 10.4049/jimmunol.1600604

S. Vermeren, K. Miles, Julia Y. Chu, D. Salter, R. Zamoyska, Mohini Gray

{"title":"PTPN22 Is a Critical Regulator of Fcγ Receptor–Mediated Neutrophil Activation","authors":"S. Vermeren, K. Miles, Julia Y. Chu, D. Salter, R. Zamoyska, Mohini Gray","doi":"10.4049/jimmunol.1600604","DOIUrl":"https://doi.org/10.4049/jimmunol.1600604","url":null,"abstract":"Neutrophils act as a first line of defense against bacterial and fungal infections, but they are also important effectors of acute and chronic inflammation. Genome-wide association studies have established that the gene encoding the protein tyrosine phosphatase nonreceptor 22 (PTPN22) makes an important contribution to susceptibility to autoimmune disease, notably rheumatoid arthritis. Although PTPN22 is most highly expressed in neutrophils, its function in these cells remains poorly characterized. We show in this article that neutrophil effector functions, including adhesion, production of reactive oxygen species, and degranulation induced by immobilized immune complexes, were reduced in Ptpn22−/− neutrophils. Tyrosine phosphorylation of Lyn and Syk was altered in Ptpn22−/− neutrophils. On stimulation with immobilized immune complexes, Ptpn22−/− neutrophils manifested reduced activation of key signaling intermediates. Ptpn22−/− mice were protected from immune complex–mediated arthritis, induced by the transfer of arthritogenic serum. In contrast, in vivo neutrophil recruitment following thioglycollate-induced peritonitis and in vitro chemotaxis were not affected by lack of PTPN22. Our data suggest an important role for PTPN22-dependent dephosphorylation events, which are required to enable full FcγR-induced activation, pointing to an important role for this molecule in neutrophil function.","PeriodicalId":310446,"journal":{"name":"The Journal of Immunology Author Choice","volume":"138 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131976680","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: 26

Eomeshi NK Cells in Human Liver Are Long-Lived and Do Not Recirculate but Can Be Replenished from the Circulation 人肝脏中嗜毒NK细胞寿命长，不循环，可从循环中补充

The Journal of Immunology Author Choice Pub Date : 2016-10-21 DOI: 10.4049/jimmunol.1601424

Antonia O. Cuff, F. Robertson, K. Stegmann, L. J. Pallett, M. Maini, B. Davidson, V. Male

引用次数: 96