Immunological Reviews最新文献_第7页

Inflammasome-mediated pyroptosis in defense against pathogenic bacteria 炎症体介导的热蛋白沉积在抵御病原菌的过程中。

IF 7.5 2区医学

Immunological Reviews Pub Date : 2024-10-15 DOI: 10.1111/imr.13408

Changhoon Oh, Todd J. Spears, Youssef Aachoui

引用次数: 0

Stellabody: A novel hexamer-promoting mutation for improved IgG potency Stellabody：一种新型六聚体促进突变，可提高 IgG 的效力。

IF 7.5 2区医学

Immunological Reviews Pub Date : 2024-10-04 DOI: 10.1111/imr.13400

Clarissa A. Whitehead, Bruce D. Wines, Anna M. Davies, James M. McDonnell, Halina M. Trist, Sandra E. Esparon, P. Mark Hogarth

{"title":"Stellabody: A novel hexamer-promoting mutation for improved IgG potency","authors":"Clarissa A. Whitehead, Bruce D. Wines, Anna M. Davies, James M. McDonnell, Halina M. Trist, Sandra E. Esparon, P. Mark Hogarth","doi":"10.1111/imr.13400","DOIUrl":"10.1111/imr.13400","url":null,"abstract":"Advances in antibody engineering are being directed at the development of next generation immunotherapeutics with improved potency. Hexamerisation of IgG is a normal physiological aspect of IgG biology and recently described mutations that facilitate this process have a substantial impact upon monoclonal antibody behavior resulting in the elicitation of dramatically enhanced complement-dependent cytotoxicity, Fc receptor function, and enhanced antigen binding effects, such as targeted receptor agonism or microbe neutralization. Whereas the discovery of IgG hexamerisation enhancing mutations has largely focused on residues with exposure at the surface of the Fc-Fc and CH2-CH3 interfaces, our unique approach is the engineering of the mostly buried residue H429 in the CH3 domain. Selective substitution at position 429 forms the basis of Stellabody technology, where the choice of amino acid results in distinct hexamerisation outcomes. H429F results in monomeric IgG that hexamerises after target binding, so called “on-target” hexamerisation, while the H429Y mutant forms pH-sensitive hexamers in-solution prior to antigen binding. Moreover, Stellabody technologies are broadly applicable across the family of antibody-based biologic therapeutics, including conventional mAbs, bispecific mAbs, and Ig-like biologics such as Fc-fusions, with applications in diverse diseases.","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"328 1","pages":"438-455"},"PeriodicalIF":7.5,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.13400","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142370416","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: 0

Using IMGT unique numbering for IG allotypes and Fc-engineered variants of effector properties and half-life of therapeutic antibodies 使用 IMGT 对 IG 所有类型和 Fc 工程变体的效应特性和治疗性抗体的半衰期进行独特编号。

IF 7.5 2区医学

Immunological Reviews Pub Date : 2024-10-04 DOI: 10.1111/imr.13399

Marie-Paule Lefranc, Gérard Lefranc

{"title":"Using IMGT unique numbering for IG allotypes and Fc-engineered variants of effector properties and half-life of therapeutic antibodies","authors":"Marie-Paule Lefranc, Gérard Lefranc","doi":"10.1111/imr.13399","DOIUrl":"10.1111/imr.13399","url":null,"abstract":"Therapeutic monoclonal antibodies (mAb) are usually of the IgG1, IgG2, and IgG4 classes, and their heavy chains may be modified by amino acid (aa) changes involved in antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), complement-dependent cytotoxicity (CDC), and/or half-life. Allotypes and Fc-engineered variants are classified using IMGT/HGNC gene nomenclature (e.g., Homo sapiens IGHG1). Allotype names follow the WHO/IMGT nomenclature. IMGT-engineered variant names use the IMGT nomenclature (e.g., Homsap G1v1), which comprises species and gene name (both abbreviated) followed by the letter v (for variant) and a number. Both allotypes and engineered variants are defined by their aa changes and positions, based on the IMGT unique numbering for C domain, identified in sequence motifs, referred to as IMGT topological motifs, as their limits and length are standardized and correspond to a structural feature (e.g., strand or loop). One hundred twenty-six variants are displayed with their type, IMGT numbering, Eu-IMGT positions, motifs before and after changes, and their property and function (effector and half-life). Three motifs characterize effector variants, CH2 1.6–3, 23-BC-41, and the FG loop, whereas three different motifs characterize half-life variants, two on CH2 13-AB-18 and 89–96 with H93, and one on CH3 the FG loop with H115.","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"328 1","pages":"473-506"},"PeriodicalIF":7.5,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.13399","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142374751","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: 0

The importance of IgG glycosylation—What did we learn after analyzing over 100,000 individuals IgG 糖基化的重要性--在分析了十多万人之后，我们学到了什么？

IF 7.5 2区医学

Immunological Reviews Pub Date : 2024-10-04 DOI: 10.1111/imr.13407

Jasminka Krištić, Gordan Lauc

{"title":"The importance of IgG glycosylation—What did we learn after analyzing over 100,000 individuals","authors":"Jasminka Krištić, Gordan Lauc","doi":"10.1111/imr.13407","DOIUrl":"10.1111/imr.13407","url":null,"abstract":"All four subclasses of immunoglobulin G (IgG) antibodies have glycan structures attached to the protein part of the IgG molecules. Glycans linked to the Fc portion of IgG are found in all IgG antibodies, while about one-fifth of IgG antibodies in plasma also have glycans attached to the Fab portion of IgG. The IgG3 subclass is characterized by more complex glycosylation compared to other IgG subclasses. In this review, we discuss the significant influence that glycans exert on the structural and functional properties of IgG. We provide a comprehensive overview of how the composition of these glycans can affect IgG's effector functions by modulating its interactions with Fcγ receptors and other molecules such as the C1q component of complement, which in turn influence various immune responses triggered by IgG, including antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). In addition, the importance of glycans for the efficacy of therapeutics like monoclonal antibodies and intravenous immunoglobulin (IVIg) therapy is discussed. Moreover, we offer insights into IgG glycosylation characteristics and roles derived from general population, disease-specific, and interventional studies. These studies indicate that IgG glycans are important biomarkers and functional effectors in health and disease.","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"328 1","pages":"143-170"},"PeriodicalIF":7.5,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.13407","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142370417","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: 0

Antibodies in neurological diseases: Established, emerging, explorative 神经系统疾病中的抗体：已有的、新出现的、探索性的。

IF 7.5 2区医学

Immunological Reviews Pub Date : 2024-10-01 DOI: 10.1111/imr.13405

Lucie Y. Li, Amelya Keles, Marie A. Homeyer, Harald Prüss

{"title":"Antibodies in neurological diseases: Established, emerging, explorative","authors":"Lucie Y. Li, Amelya Keles, Marie A. Homeyer, Harald Prüss","doi":"10.1111/imr.13405","DOIUrl":"10.1111/imr.13405","url":null,"abstract":"Within a few years, autoantibodies targeting the nervous system resulted in a novel disease classification. For several of them, which we termed ‘established’, direct pathogenicity has been proven and now guides diagnostic pathways and early immunotherapy. For a rapidly growing number of further anti-neuronal autoantibodies, the role in disease is less clear. Increasing evidence suggests that they could contribute to disease, by playing a modulating role on brain function. We therefore suggest a three-level classification of neurological autoantibodies according to the degree of experimentally proven pathogenicity and strength of clinical association: established, emerging, explorative. This may facilitate focusing on clinical constellations in which autoantibody-mediated mechanisms have not been assumed previously, including autoimmune psychosis and dementia, cognitive impairment in cancer, and neurodegenerative diseases. Based on recent data reviewed here, humoral autoimmunity may represent an additional “super-system” for brain health. The “brain antibody-ome”, that is, the composition of thousands of anti-neuronal autoantibodies, may shape neuronal function not only in disease, but even in healthy aging. Towards this novel concept, extensive research will have to elucidate pathogenicity from the atomic to the clinical level, autoantibody by autoantibody. Such profiling can uncover novel biomarkers, enhance our understanding of underlying mechanisms, and identify selective therapies.","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"328 1","pages":"283-299"},"PeriodicalIF":7.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.13405","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337941","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: 0

Molecular mechanisms of emerging inflammasome complexes and their activation and signaling in inflammation and pyroptosis 新出现的炎症小体复合物及其在炎症和脓毒症中的激活和信号传导的分子机制。

IF 7.5 2区医学

Immunological Reviews Pub Date : 2024-10-01 DOI: 10.1111/imr.13406

Abhimanu Pandey, Zheyi Li, Manjul Gautam, Aritra Ghosh, Si Ming Man

{"title":"Molecular mechanisms of emerging inflammasome complexes and their activation and signaling in inflammation and pyroptosis","authors":"Abhimanu Pandey, Zheyi Li, Manjul Gautam, Aritra Ghosh, Si Ming Man","doi":"10.1111/imr.13406","DOIUrl":"10.1111/imr.13406","url":null,"abstract":"Inflammasomes are multi-protein complexes that assemble within the cytoplasm of mammalian cells in response to pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs), driving the secretion of the pro-inflammatory cytokines IL-1β and IL-18, and pyroptosis. The best-characterized inflammasome complexes are the NLRP3, NAIP-NLRC4, NLRP1, AIM2, and Pyrin canonical caspase-1-containing inflammasomes, and the caspase-11 non-canonical inflammasome. Newer inflammasome sensor proteins have been identified, including NLRP6, NLRP7, NLRP9, NLRP10, NLRP11, NLRP12, CARD8, and MxA. These inflammasome sensors can sense PAMPs from bacteria, viruses and protozoa, or DAMPs in the form of mitochondrial damage, ROS, stress and heme. The mechanisms of action, physiological relevance, consequences in human diseases, and avenues for therapeutic intervention for these novel inflammasomes are beginning to be realized. Here, we discuss these emerging inflammasome complexes and their putative activation mechanisms, molecular and signaling pathways, and physiological roles in health and disease.","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"329 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337945","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: 0

Fc gamma receptors: Their evolution, genomic architecture, genetic variation, and impact on human disease Fc γ 受体：它们的进化、基因组结构、遗传变异以及对人类疾病的影响。

IF 7.5 2区医学

Immunological Reviews Pub Date : 2024-09-30 DOI: 10.1111/imr.13401

Sarah Frampton, Rosanna Smith, Lili Ferson, Jane Gibson, Edward J. Hollox, Mark S. Cragg, Jonathan C. Strefford

{"title":"Fc gamma receptors: Their evolution, genomic architecture, genetic variation, and impact on human disease","authors":"Sarah Frampton, Rosanna Smith, Lili Ferson, Jane Gibson, Edward J. Hollox, Mark S. Cragg, Jonathan C. Strefford","doi":"10.1111/imr.13401","DOIUrl":"10.1111/imr.13401","url":null,"abstract":"Fc gamma receptors (FcγRs) are a family of receptors that bind IgG antibodies and interface at the junction of humoral and innate immunity. Precise regulation of receptor expression provides the necessary balance to achieve healthy immune homeostasis by establishing an appropriate immune threshold to limit autoimmunity but respond effectively to infection. The underlying genetics of the FCGR gene family are central to achieving this immune threshold by regulating affinity for IgG, signaling efficacy, and receptor expression. The FCGR gene locus was duplicated during evolution, retaining very high homology and resulting in a genomic region that is technically difficult to study. Here, we review the recent evolution of the gene family in mammals, its complexity and variation through copy number variation and single-nucleotide polymorphism, and impact of these on disease incidence, resolution, and therapeutic antibody efficacy. We also discuss the progress and limitations of current approaches to study the region and emphasize how new genomics technologies will likely resolve much of the current confusion in the field. This will lead to definitive conclusions on the impact of genetic variation within the FCGR gene locus on immune function and disease.","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"328 1","pages":"65-97"},"PeriodicalIF":7.5,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.13401","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337942","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: 0

Protective role of antibodies in enteric virus infections: Lessons from primary and secondary immune deficiencies 抗体在肠道病毒感染中的保护作用：原发性和继发性免疫缺陷的教训。

IF 7.5 2区医学

Immunological Reviews Pub Date : 2024-09-28 DOI: 10.1111/imr.13402

Quentin Riller, Muriel Schmutz, Jacques Fourgeaud, Alain Fischer, Bénédicte Neven

{"title":"Protective role of antibodies in enteric virus infections: Lessons from primary and secondary immune deficiencies","authors":"Quentin Riller, Muriel Schmutz, Jacques Fourgeaud, Alain Fischer, Bénédicte Neven","doi":"10.1111/imr.13402","DOIUrl":"10.1111/imr.13402","url":null,"abstract":"Enteric viruses are the main cause of acute gastroenteritis worldwide with a significant morbidity and mortality, especially among children and aged adults. Some enteric viruses also cause disseminated infections and severe neurological manifestations such as poliomyelitis. Protective immunity against these viruses is not well understood in humans, with most knowledge coming from animal models, although the development of poliovirus and rotavirus vaccines has extended our knowledge. In a classical view, innate immunity involves the recognition of foreign DNA or RNA by pathogen recognition receptors leading to the production of interferons and other inflammatory cytokines. Antigen uptake and presentation to T cells and B cells then activate adaptive immunity and, in the case of the mucosal immunity, induce the secretion of dimeric IgA, the more potent immunoglobulins in viral neutralization. The study of Inborn errors of immunity (IEIs) offers a natural opportunity to study nonredundant immunity toward pathogens. In the case of enteric viruses, patients with a defective production of antibodies are at risk of developing neurological complications. Moreover, a recent description of patients with low or absent antibody production with protracted enteric viral infections associated with hepatitis reinforces the prominent role of B cells and immunoglobulins in the control of enteric virus.","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"328 1","pages":"243-264"},"PeriodicalIF":7.5,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.13402","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337946","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: 0

From fat to fire: The lipid–inflammasome connection 从脂肪到火焰脂质-炎症体之间的联系

IF 7.5 2区医学

Immunological Reviews Pub Date : 2024-09-27 DOI: 10.1111/imr.13403

Paras K. Anand

{"title":"From fat to fire: The lipid–inflammasome connection","authors":"Paras K. Anand","doi":"10.1111/imr.13403","DOIUrl":"10.1111/imr.13403","url":null,"abstract":"Inflammasomes are multiprotein complexes that play a crucial role in regulating immune responses by governing the activation of Caspase-1, the secretion of pro-inflammatory cytokines, and the induction of inflammatory cell death, pyroptosis. The inflammasomes are pivotal in effective host defense against a range of pathogens. Yet, overt activation of inflammasome signaling can be detrimental. The most well-studied NLRP3 inflammasome has the ability to detect a variety of stimuli including pathogen-associated molecular patterns, environmental irritants, and endogenous stimuli released from dying cells. Additionally, NLRP3 acts as a key sensor of cellular homeostasis and can be activated by disturbances in diverse metabolic pathways. Consequently, NLRP3 is considered a key player linking metabolic dysregulation to numerous inflammatory disorders such as gout, diabetes, and atherosclerosis. Recently, compelling studies have highlighted a connection between lipids and the regulation of NLRP3 inflammasome. Lipids are integral to cellular processes that serve not only in maintaining the structural integrity and subcellular compartmentalization, but also in contributing to physiological equilibrium. Certain lipid species are known to define NLRP3 subcellular localization, therefore directly influencing the site of inflammasome assembly and activation. For instance, phosphatidylinositol 4-phosphate plays a crucial role in NLRP3 localization to the trans Golgi network. Moreover, new evidence has demonstrated the roles of lipid biosynthesis and trafficking in activation of the NLRP3 inflammasome. This review summarizes and discusses these emerging and varied roles of lipid metabolism in inflammasome activation. A deeper understanding of lipid-inflammasome interactions may open new avenues for therapeutic interventions to prevent or treat chronic inflammatory and autoimmune conditions.","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"329 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337943","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: 0

Immunomodulatory and anti-inflammatory properties of immunoglobulin G antibodies 免疫球蛋白 G 抗体的免疫调节和抗炎特性。

IF 7.5 2区医学

Immunological Reviews Pub Date : 2024-09-27 DOI: 10.1111/imr.13404

Marjan Hematianlarki, Falk Nimmerjahn

{"title":"Immunomodulatory and anti-inflammatory properties of immunoglobulin G antibodies","authors":"Marjan Hematianlarki, Falk Nimmerjahn","doi":"10.1111/imr.13404","DOIUrl":"10.1111/imr.13404","url":null,"abstract":"Antibodies provide an essential layer of protection from infection and reinfection with microbial pathogens. An impaired ability to produce antibodies results in immunodeficiency and necessitates the constant substitution with pooled serum antibodies from healthy donors. Among the five antibody isotypes in humans and mice, immunoglobulin G (IgG) antibodies are the most potent anti-microbial antibody isotype due to their long half-life, their ability to penetrate almost all tissues and due to their ability to trigger a wide variety of effector functions. Of note, individuals suffering from IgG deficiency frequently produce self-reactive antibodies, suggesting that a normal serum IgG level also may contribute to maintaining self-tolerance. Indeed, the substitution of immunodeficient patients with pooled serum IgG fractions from healthy donors, also referred to as intravenous immunoglobulin G (IVIg) therapy, not only protects the patient from infection but also diminishes autoantibody induced pathology, providing more direct evidence that IgG antibodies play an active role in maintaining tolerance during the steady state and during resolution of inflammation. The aim of this review is to discuss different conceptual models that may explain how serum IgG or IVIg can contribute to maintaining a balanced immune response. We will focus on pathways depending on the IgG fragment crystallizable (Fc) as pre-clinical data in various mouse model systems as well as human clinical data have demonstrated that the IgG Fc-domain recapitulates the ability of intact IVIg with respect to its ability to trigger resolution of inflammation. We will further discuss how the findings already have or are in the process of being translated to novel therapeutic approaches to substitute IVIg in treating autoimmune inflammation.","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"328 1","pages":"372-386"},"PeriodicalIF":7.5,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.13404","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337944","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: 0