Immunological Reviews最新文献_第10页

Physiology and pathology of the C3 amplification cycle: A retrospective C3扩增周期的生理和病理:回顾性分析

IF 8.7 2区医学

Immunological Reviews Pub Date : 2022-11-21 DOI: 10.1111/imr.13165

Keith Peters

引用次数: 2

The neutrophil: A key resourceful agent in immune-mediated vasculitis 中性粒细胞:免疫介导的血管炎的关键因子

IF 8.7 2区医学

Immunological Reviews Pub Date : 2022-11-21 DOI: 10.1111/imr.13170

Karen Aymonnier, Jennifer Amsler, Peter Lamprecht, Alan Salama, Véronique Witko-Sarsat

{"title":"The neutrophil: A key resourceful agent in immune-mediated vasculitis","authors":"Karen Aymonnier, Jennifer Amsler, Peter Lamprecht, Alan Salama, Véronique Witko-Sarsat","doi":"10.1111/imr.13170","DOIUrl":"https://doi.org/10.1111/imr.13170","url":null,"abstract":"The term “vasculitis” refers to a group of rare immune-mediated diseases characterized by the dysregulated immune system attacking blood vessels located in any organ of the body, including the skin, lungs, and kidneys. Vasculitides are classified according to the size of the vessel that is affected. Although this observation is not specific to small-, medium-, or large-vessel vasculitides, patients show a high circulating neutrophil-to-lymphocyte ratio, suggesting the direct or indirect involvement of neutrophils in these diseases. As first responders to infection or inflammation, neutrophils release cytotoxic mediators, including reactive oxygen species, proteases, and neutrophil extracellular traps. If not controlled, this dangerous arsenal can injure the vascular system, which acts as the main transport route for neutrophils, thereby amplifying the initial inflammatory stimulus and the recruitment of immune cells. This review highlights the ability of neutrophils to “set the tone” for immune cells and other cells in the vessel wall. Considering both their long-established and newly described roles, we extend their functions far beyond their direct host-damaging potential. We also review the roles of neutrophils in various types of primary vasculitis, including immune complex vasculitis, anti-neutrophil cytoplasmic antibody-associated vasculitis, polyarteritis nodosa, Kawasaki disease, giant cell arteritis, Takayasu arteritis, and Behçet's disease.","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"314 1","pages":"326-356"},"PeriodicalIF":8.7,"publicationDate":"2022-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.13170","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5751091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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: 3

Neutrophils are gatekeepers of mucosal immunity 中性粒细胞是粘膜免疫的守门人

IF 8.7 2区医学

Immunological Reviews Pub Date : 2022-11-20 DOI: 10.1111/imr.13171

Lakmali M. Silva, Tae Sung Kim, Niki M. Moutsopoulos

引用次数: 4

Protein therapeutics and their lessons: Expect the unexpected when inhibiting the multi-protein cascade of the complement system 蛋白质疗法及其经验教训:当抑制补体系统的多蛋白级联反应时，期待意想不到的结果

IF 8.7 2区医学

Immunological Reviews Pub Date : 2022-11-18 DOI: 10.1111/imr.13164

Christoph Q. Schmidt, Richard J. H. Smith

{"title":"Protein therapeutics and their lessons: Expect the unexpected when inhibiting the multi-protein cascade of the complement system","authors":"Christoph Q. Schmidt, Richard J. H. Smith","doi":"10.1111/imr.13164","DOIUrl":"https://doi.org/10.1111/imr.13164","url":null,"abstract":"Over a century after the discovery of the complement system, the first complement therapeutic was approved for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). It was a long-acting monoclonal antibody (aka 5G1-1, 5G1.1, h5G1.1, and now known as eculizumab) that targets C5, specifically preventing the generation of C5a, a potent anaphylatoxin, and C5b, the first step in the eventual formation of membrane attack complex. The enormous clinical and financial success of eculizumab across four diseases (PNH, atypical hemolytic uremic syndrome (aHUS), myasthenia gravis (MG), and anti-aquaporin-4 (AQP4) antibody-positive neuromyelitis optica spectrum disorder (NMOSD)) has fueled a surge in complement therapeutics, especially targeting diseases with an underlying complement pathophysiology for which anti-C5 therapy is ineffective. Intensive research has also uncovered challenges that arise from C5 blockade. For example, PNH patients can still face extravascular hemolysis or pharmacodynamic breakthrough of complement suppression during complement-amplifying conditions. These “side” effects of a stoichiometric inhibitor like eculizumab were unexpected and are incompatible with some of our accepted knowledge of the complement cascade. And they are not unique to C5 inhibition. Indeed, “exceptions” to the rules of complement biology abound and have led to unprecedented and surprising insights. In this review, we will describe initial, present and future aspects of protein inhibitors of the complement cascade, highlighting unexpected findings that are redefining some of the mechanistic foundations upon which the complement cascade is organized.","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"313 1","pages":"376-401"},"PeriodicalIF":8.7,"publicationDate":"2022-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.13164","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5919177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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: 5

The Factor H protein family: The switchers of the complement alternative pathway 因子H蛋白家族:补体替代途径的开关

IF 8.7 2区医学

Immunological Reviews Pub Date : 2022-11-16 DOI: 10.1111/imr.13166

Laura Lucientes-Continente, Bárbara Márquez-Tirado, Elena Goicoechea de Jorge

{"title":"The Factor H protein family: The switchers of the complement alternative pathway","authors":"Laura Lucientes-Continente, Bárbara Márquez-Tirado, Elena Goicoechea de Jorge","doi":"10.1111/imr.13166","DOIUrl":"https://doi.org/10.1111/imr.13166","url":null,"abstract":"The factor H (FH) protein family is emerging as a complex network of proteins controlling the fate of the complement alternative pathway (AP) and dictating susceptibility to a wide range of diseases including infectious, inflammatory, autoimmune, and degenerative diseases and cancer. Composed, in man, of seven highly related proteins, FH, factor H-like 1, and 5 factor H-related proteins, some of the FH family proteins are devoted to down-regulating the AP, while others exert an opposite function by promoting AP activation. Recent findings have provided insights into the molecular mechanisms defining their biological roles and their pathogenicity, illustrating the relevance that the balance between the regulators and the activators within this protein family has in defining the outcome of complement activation on cell surfaces. In this review we will discuss the emerging roles of the factor H protein family, their impact in the complement cascade, and their involvement in the pathogenesis of complement-mediated diseases associated with the AP dysregulation.","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"313 1","pages":"25-45"},"PeriodicalIF":8.7,"publicationDate":"2022-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.13166","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5691158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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: 16

Alternative pathway activation in pregnancy, a measured amount “complements” a successful pregnancy, too much results in adverse events 妊娠期替代通路激活，适量“补充”成功妊娠，过多会导致不良事件

IF 8.7 2区医学

Immunological Reviews Pub Date : 2022-11-15 DOI: 10.1111/imr.13169

Kate Smith-Jackson, Richard Alexander Harrison

{"title":"Alternative pathway activation in pregnancy, a measured amount “complements” a successful pregnancy, too much results in adverse events","authors":"Kate Smith-Jackson, Richard Alexander Harrison","doi":"10.1111/imr.13169","DOIUrl":"https://doi.org/10.1111/imr.13169","url":null,"abstract":"During pregnancy, the maternal host must adapt in order to enable growth of the fetus. These changes affect all organ systems and are designed both to protect the fetus and to minimize risk to the mother. One of the most prominent adaptations involves the immune system. The semi-allogenic fetoplacental unit has non-self components and must be protected against attack from the host. This requires both attenuation of adaptive immunity and protection from innate immune defense mechanisms. One of the key innate immune players is complement, and it is important that the fetoplacental unit is not identified as non-self and subjected to complement attack. Adaptation of the complement response must, however, be managed in such a way that maternal protection against infection is not compromised. As the complement system also plays a significant facilitating role in many of the stages of a normal pregnancy, it is also important that any necessary adaptation to accommodate the semi-allogenic aspects of the fetoplacental unit does not compromise this. In this review, both the physiological role of the alternative pathway of complement in facilitating a normal pregnancy, and its detrimental participation in pregnancy-specific disorders, are discussed.","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"313 1","pages":"298-319"},"PeriodicalIF":8.7,"publicationDate":"2022-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.13169","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6155617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Human neutrophils ≠ murine neutrophils: Does it matter? 人类中性粒细胞≠小鼠中性粒细胞:这有关系吗?

IF 8.7 2区医学

Immunological Reviews Pub Date : 2022-11-15 DOI: 10.1111/imr.13154

William M. Nauseef

{"title":"Human neutrophils \u0000 \u0000 \u0000 ≠\u0000 \u0000 murine neutrophils: Does it matter?","authors":"William M. Nauseef","doi":"10.1111/imr.13154","DOIUrl":"https://doi.org/10.1111/imr.13154","url":null,"abstract":"Human and murine neutrophils differ with respect to representation in blood, receptors, nuclear morphology, signaling pathways, granule proteins, NADPH oxidase regulation, magnitude of oxidant and hypochlorous acid production, and their repertoire of secreted molecules. These differences often matter and can undermine extrapolations from murine studies to clinical care, as illustrated by several failed therapeutic interventions based on mouse models. Likewise, coevolution of host and pathogen undercuts fidelity of murine models of neutrophil-predominant human infections. However, murine systems that accurately model the human condition can yield insights into human biology difficult to obtain otherwise. The challenge for investigators who employ murine systems is to distinguish models from pretenders and to know when the mouse provides biologically accurate insights. Testing with human neutrophils observations made in murine systems would provide a safeguard but is not always possible. At a minimum, studies that use exclusively murine neutrophils should have accurate titles supported by data and restrict conclusions to murine neutrophils and not encompass all neutrophils. For now, the integration of evidence from studies of neutrophil biology performed using valid murine models coupled with testing in vitro of human neutrophils combines the best of both approaches to elucidate the mysteries of human neutrophil biology.","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"314 1","pages":"442-456"},"PeriodicalIF":8.7,"publicationDate":"2022-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.13154","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5874585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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: 9

Gene targeting as a therapeutic avenue in diseases mediated by the complement alternative pathway 基因靶向作为补体替代途径介导疾病的治疗途径

IF 8.7 2区医学

Immunological Reviews Pub Date : 2022-11-12 DOI: 10.1111/imr.13149

Anna K Dreismann, Thomas M Hallam, Lawrence CS Tam, Calvin V Nguyen, Jane P Hughes, Scott Ellis, Claire L Harris

{"title":"Gene targeting as a therapeutic avenue in diseases mediated by the complement alternative pathway","authors":"Anna K Dreismann, Thomas M Hallam, Lawrence CS Tam, Calvin V Nguyen, Jane P Hughes, Scott Ellis, Claire L Harris","doi":"10.1111/imr.13149","DOIUrl":"https://doi.org/10.1111/imr.13149","url":null,"abstract":"The complement alternative pathway (AP) is implicated in numerous diseases affecting many organs, ranging from the rare hematological disease paroxysmal nocturnal hemoglobinuria (PNH), to the common blinding disease age-related macular degeneration (AMD). Critically, the AP amplifies any activating trigger driving a downstream inflammatory response; thus, components of the pathway have become targets for drugs of varying modality. Recent validation from clinical trials using drug modalities such as inhibitory antibodies has paved the path for gene targeting of the AP or downstream effectors. Gene targeting in the complement field currently focuses on supplementation or suppression of complement regulators in AMD and PNH, largely because the eye and liver are highly amenable to drug delivery through local (eye) or systemic (liver) routes. Targeting the liver could facilitate treatment of numerous diseases as this organ generates most of the systemic complement pool. This review explains key concepts of RNA and DNA targeting and discusses assets in clinical development for the treatment of diseases driven by the alternative pathway, including the RNA-targeting therapeutics ALN-CC5, ARO-C3, and IONIS-FB-LRX, and the gene therapies GT005 and HMR59. These therapies are but the spearhead of potential drug candidates that might revolutionize the field in coming years.","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"313 1","pages":"402-419"},"PeriodicalIF":8.7,"publicationDate":"2022-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.13149","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6108124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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: 8

The susceptibility of the kidney to alternative pathway activation—A hypothesis 肾脏对替代通路激活的易感性——一种假说

IF 8.7 2区医学

Immunological Reviews Pub Date : 2022-11-12 DOI: 10.1111/imr.13168

Joshua M. Thurman, Richard A. Harrison

{"title":"The susceptibility of the kidney to alternative pathway activation—A hypothesis","authors":"Joshua M. Thurman, Richard A. Harrison","doi":"10.1111/imr.13168","DOIUrl":"https://doi.org/10.1111/imr.13168","url":null,"abstract":"<div>\u0000 \u0000 The glomerulus is often the prime target of dysregulated alternative pathway (AP) activation. In particular, AP activation is the key driver of two severe kidney diseases: atypical hemolytic uremic syndrome and C3 glomerulopathy. Both conditions are associated with a variety of predisposing molecular defects in AP regulation, such as genetic variants in complement regulators, autoantibodies targeting AP proteins, or autoantibodies that stabilize the AP convertases (C3- and C5-activating enzymes). It is noteworthy that these are systemic AP defects, yet in both diseases pathologic complement activation primarily affects the kidneys. In particular, AP activation is often limited to the glomerular capillaries. This tropism of AP-mediated inflammation for the glomerulus points to a unique interaction between AP proteins in plasma and this particular anatomic structure. In this review, we discuss the pre-clinical and clinical data linking the molecular causes of aberrant control of the AP with activation in the glomerulus, and the possible causes of this tropism. Based on these data, we propose a model for why the kidney is so uniquely and frequently targeted in patients with AP defects. Finally, we discuss possible strategies for preventing pathologic AP activation in the kidney.\u0000 </div>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"313 1","pages":"327-338"},"PeriodicalIF":8.7,"publicationDate":"2022-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6108131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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: 4

Kidney diseases 肾脏疾病

IF 8.7 2区医学

Immunological Reviews Pub Date : 2022-11-12 DOI: 10.1111/imr.13167

Erica Daina, Monica Cortinovis, Giuseppe Remuzzi

{"title":"Kidney diseases","authors":"Erica Daina, Monica Cortinovis, Giuseppe Remuzzi","doi":"10.1111/imr.13167","DOIUrl":"https://doi.org/10.1111/imr.13167","url":null,"abstract":"Dysregulation and accelerated activation of the alternative pathway (AP) of complement is known to cause or accentuate several pathologic conditions in which kidney injury leads to the appearance of hematuria and proteinuria and ultimately to the development of chronic renal failure. Multiple genetic and acquired defects involving plasma- and membrane-associated proteins are probably necessary to impair the protection of host tissues and to confer a significant predisposition to AP-mediated kidney diseases. This review aims to explore how our current understanding will make it possible to identify the mechanisms that underlie AP-mediated kidney diseases and to discuss the available clinical evidence that supports complement-directed therapies. Although the value of limiting uncontrolled complement activation has long been recognized, incorporating complement-targeted treatments into clinical use has proved challenging. Availability of anti-complement therapy has dramatically transformed the outcome of atypical hemolytic uremic syndrome, one of the most severe kidney diseases. Innovative drugs that directly counteract AP dysregulation have also opened new perspectives for the management of other kidney diseases in which complement activation is involved. However, gained experience indicates that the choice of drug should be tailored to each patient's characteristics, including clinical, histologic, genetic, and biochemical parameters. Successfully treating patients requires further research in the field and close collaboration between clinicians and researchers who have special expertise in the complement system.","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"313 1","pages":"239-261"},"PeriodicalIF":8.7,"publicationDate":"2022-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.13167","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6228142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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: 1