Immunological Reviews最新文献

{"title":"The Effector Functions of Antibodies","authors":"Marc Daëron","doi":"10.1111/imr.13428","DOIUrl":"10.1111/imr.13428","url":null,"abstract":"<p>“Antibody” is one of those specialists' words that became common language. Everyone knows that antibodies protect against infectious diseases, especially since the COVID-19 pandemic swept across the world. Everyone, or almost, even knows what antibodies look like. Their anthropomorphic Y shape has become an iconic symbol that most societies of immunology have included in their logo. What antibodies actually are, however, is not so clear in everyone's mind, as judged by media which often confuse serum with vaccine. What antibodies do and how they work is another question. Their well-known ability to recognize specific antigens with each of their two “arms” is often thought to be enough to protect; even by scientists, sometimes by immunologists. Whatever how, antibodies protect, and when they have pathogenic effects, these are viewed as the unfortunate consequences of targeting errors such as in allergic and autoimmune diseases, or collateral damages such as in inflammatory diseases.</p><p>Antibodies are also well known as tools. Due to their exquisite specificity, antibodies have proven unrivaled diagnostic tools and they are used in a variety of techniques adopted by all medical disciplines and beyond. Due to their powerful biological properties, antibodies have been increasingly used as therapeutic tools with amazing efficiencies. This is not new: antibodies saved thousands of children from diphtheria and many more wounded soldiers from tetanus at the beginning of the 20th century, when they were nothing but elusive substances in immune serum. They are well-known molecules now and, as serum therapy for deadly infectious diseases yesterday, humanized monoclonal antibodies have provided long-sought cures for cancers with a poor prognosis today. Not without side effects, though. But antibodies can be engineered genetically to enhance their expected effects and to decrease their unwanted effects.</p><p>Why, therefore, put together another series of review articles on such well-known molecules? As stated in its title, this volume of <i>Immunological Reviews</i> is focused on the <i>effector functions</i> of antibodies. Antibodies are bi-functional molecules: They can not only recognize antigens; they can also act on them. How they do so is poorly known by immunologists, except those who work specifically on the subject. Yet, antibodies are the main effectors of adaptive immunity, at least quantitatively: 10 mg/mL IgG and 2–3 mg/mL IgA circulate in the blood stream—and much more are present in tissues since 80% immunoglobulin-secreting plasma cells of the whole body produce mucosal IgA. How do these antibodies deal with pathogens and commensals? How can they both prevent infections and tolerate microbiotas without inducing devastating inflammatory reactions? How antibodies induced by vaccines exert their protective effects?</p><p>This volume deals with the effector functions of antibodies not only in health, but also in disease. If they protect aga","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"328 1","pages":"6-12"},"PeriodicalIF":7.5,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.13428","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805741","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}

{"title":"Fc Effector Function of Immune Checkpoint Blocking Antibodies in Oncology","authors":"Romane Martineau,&nbsp;Sandrine Susini,&nbsp;Aurelien Marabelle","doi":"10.1111/imr.13427","DOIUrl":"10.1111/imr.13427","url":null,"abstract":"<p>Antagonistic monoclonal antibodies (mAbs) targeting inhibitory immune checkpoints have revolutionized the field of oncology. CTLA-4, PD-1, and LAG3 are three co-inhibitory receptors, which can be expressed by subsets of T cells and which play a role in the regulation of adaptive immune responses. Blocking these immune checkpoints receptors (or their ligands) with antagonistic antibodies can lead to tumor regressions and lasting remissions in some patients with cancer. Two anti-CTLA4, six anti-PD1, three anti-PD-L1, and one anti-LAG3 antibodies are currently approved by the FDA and EMA. Their mechanism of action, safety, and efficacy are linked to their affinity with Fc gamma receptors (FcγR) (so called “effector functions”). The anti-CTLA-4 antibodies ipilimumab (IgG1) and tremilimumab (IgG2a), and the anti-PD-L1 avelumab (IgG1) have isotypes with high affinity for activating FcγR and thereby can induce ADCC/ADCP. The effector function is required for the in vivo efficacy of anti-CTLA4 antibodies. For anti-PD(L)1 antibodies, where a pure antagonistic function (“checkpoint blockade”) is sufficient, some mAbs are IgG1 but have been mutated in their Fc sequence (e.g., durvalumab and atezolizumab) or are IgG4 (e.g., nivolumab and pembrolizumab) to have low affinity for FcγR. Here, we review the impact of FcγR effector function on immune checkpoint blockers safety and efficacy in oncology.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"328 1","pages":"334-349"},"PeriodicalIF":7.5,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.13427","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811691","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}

{"title":"Established and Emerging Roles of DEAD/H-Box Helicases in Regulating Infection and Immunity.","authors":"Michael Parthun, Matthew E Long, Emily A Hemann","doi":"10.1111/imr.13426","DOIUrl":"https://doi.org/10.1111/imr.13426","url":null,"abstract":"<p><p>The sensing of nucleic acids by DEAD/H-box helicases, specifically retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated protein 5 (MDA5), plays a critical role in inducing antiviral immunity following infection. However, this DEAD/H-box helicase family includes many additional proteins whose immune functions have not been investigated. While numerous DEAD/H-box helicases contribute to antiviral immunity, they employ diverse mechanisms beyond the direct sensing of nucleic acids. Some members have also been identified to play proviral (promoting virus replication/propagation) roles during infections, regulate other non-viral infections, and contribute to the regulation of autoimmunity and cancer. This review synthesizes the known and emerging functions of the broader DEAD/H-box helicase family in immune regulation and highlights ongoing efforts to target these proteins therapeutically.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142764932","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}

{"title":"Immunoglobulin A Antibodies: From Protection to Harmful Roles","authors":"Patrick J. Gleeson,&nbsp;Niels O. S. Camara,&nbsp;Pierre Launay,&nbsp;Agnès Lehuen,&nbsp;Renato C. Monteiro","doi":"10.1111/imr.13424","DOIUrl":"10.1111/imr.13424","url":null,"abstract":"<p>Immunoglobulin A (IgA) is the most abundantly produced antibody in humans. IgA is a unique class of immunoglobulin due to its multiple molecular forms, and a defining difference between the two subclasses: IgA1 has a long hinge-region that is heavily O-glycosylated, whereas the IgA2 hinge-region is shorter but resistant to bacterial proteases prevalent at mucosal sites. IgA is essential for immune homeostasis and education. Mucosal IgA plays a crucial role in maintaining the integrity of the mucosal barrier by immune exclusion of pathobionts while facilitating colonization with certain commensals; a large part of the gut microbiota is coated with IgA. In the circulation, monomeric IgA that has not been engaged by antigen plays a discrete role in dampening inflammatory responses. Protective and harmful roles of IgA have been studied over several decades, but a new understanding of the complex role of this immunoglobulin in health and disease has been provided by recent studies. Here, we discuss the physiological and pathological roles of IgA with a special focus on the gut, kidneys, and autoimmunity. We also discuss new IgA-based therapeutic approaches.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"328 1","pages":"171-191"},"PeriodicalIF":7.5,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.13424","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692267","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}

{"title":"How Technical Advances Changed the Concept of Antibodies","authors":"Bartlomiej Swiatczak,&nbsp;Gregor P. Greslehner,&nbsp;Martin Zach","doi":"10.1111/imr.13425","DOIUrl":"10.1111/imr.13425","url":null,"abstract":"<div>\u0000 \u0000 <p>Shaped by advances in scientific instrumentation and experimental techniques, the concept of antibody has undergone profound transformations throughout the history of immunology. Serological assays, separation techniques, protein fragmentation techniques, molecular biology techniques, and other methodological innovations did not only serve to produce data on the structure and function of these molecules but, by framing antibodies into a unique facet of experimental investigation, were effectively redefining and reconceptualizing these molecules for the scientific community. The characteristics and properties of antibodies observed in experimental settings were often directly extrapolated to their presumed nature in living organisms, as exemplified by the literal identification of antibodies with a gamma electrophoretic fraction in the 1930s. Stemming from parallel advances in related fields such as molecular biology and biochemistry, the introduction of novel techniques was driving shifts in the field of immunology, establishing novel frameworks of theoretical conceptualization and understanding. Technological innovation in experimental techniques continues to shape our view of these molecules, driving progress in both basic immunology and therapeutic applications.</p>\u0000 </div>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"328 1","pages":"39-48"},"PeriodicalIF":7.5,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680034","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}

{"title":"Lessons Learned From Clinical Trials of Immunotherapeutics for COVID-19.","authors":"Inyeong Lee, Christopher R Lupfer","doi":"10.1111/imr.13422","DOIUrl":"https://doi.org/10.1111/imr.13422","url":null,"abstract":"<p><p>The COVID-19 pandemic caused by the SARS-CoV-2 virus was arguably one of the worst public health disasters of the last 100 years. As many infectious disease experts were focused on influenza, MERS, ZIKA, or Ebola as potential pandemic-causing agents, SARS-CoV-2 appeared to come from nowhere and spread rapidly. As with any zoonotic agent, the initial pathogen was able to transmit to a new host (humans), but it was poorly adapted to the immune environment of the new host and resulted in a maladapted immune response. As the host-pathogen interaction evolved, subsequent variants of SARS-CoV-2 became less pathogenic and acquired immunity in the host provided protection, at least partial protection, to new variants. As the host-pathogen interaction has changed since the beginning of the pandemic, it is possible the clinical results discussed here may not be applicable today as they were at the start of the pandemic. With this caveat in mind, we present an overview of the immune response of severe COVID-19 from a clinical research perspective and examine clinical trials utilizing immunomodulating agents to further elucidate the importance of hyperinflammation as a factor contributing to severe COVID-19 disease.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643550","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}

{"title":"Balanced regulation of ROS production and inflammasome activation in preventing early development of colorectal cancer.","authors":"Longjun Li, Tao Xu, Xiaopeng Qi","doi":"10.1111/imr.13417","DOIUrl":"https://doi.org/10.1111/imr.13417","url":null,"abstract":"<p><p>Reactive oxygen species (ROS) production and inflammasome activation are the key components of the innate immune response to microbial infection and sterile insults. ROS are at the intersection of inflammation and immunity during cancer development. Balanced regulation of ROS production and inflammasome activation serves as the central hub of innate immunity, determining whether a cell will survive or undergo cell death. However, the mechanisms underlying this balanced regulation remain unclear. Mitochondria and NADPH oxidases are the two major sources of ROS production. Recently, NCF4, a component of the NADPH oxidase complex that primarily contributes to ROS generation in phagocytes, was reported to balance ROS production and inflammasome activation in macrophages. The phosphorylation and puncta distribution of NCF4 shifts from the membrane-bound NADPH complex to the perinuclear region, promoting ASC speck formation and inflammasome activation, which triggers downstream IL-18-IFN-γ signaling to prevent the progression of colorectal cancer (CRC). Here, we review ROS signaling and inflammasome activation studies in colitis-associated CRC and propose that NCF4 acts as a ROS sensor that balances ROS production and inflammasome activation. In addition, NCF4 is a susceptibility gene for Crohn's disease (CD) and CRC. We discuss the evidence demonstrating NCF4's crucial role in facilitating cell-cell contact between immune cells and intestinal cells, and mediating the paracrine effects of inflammatory cytokines and ROS. This coordination of the signaling network helps create a robust immune microenvironment that effectively prevents epithelial cell mutagenesis and tumorigenesis during the early stage of colitis-associated CRC.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612331","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}

{"title":"Role of inflammasomes and neuroinflammation in epilepsy.","authors":"Ava Hollis, John R Lukens","doi":"10.1111/imr.13421","DOIUrl":"https://doi.org/10.1111/imr.13421","url":null,"abstract":"<p><p>Epilepsy is a brain disorder characterized by recurrent seizures, which are brief episodes of abnormal electrical activity in the brain and involuntary movement that can lead to physical injury and loss of consciousness. Seizures are canonically accompanied by increased inflammatory cytokine production that promotes neuroinflammation, brain pathology, and seizure propagation. Understanding the source of pro-inflammatory cytokines which promote seizure pathogenesis could be a gateway to precision epilepsy drug design. This review discusses the inflammasome in epilepsy including its role in seizure propagation and negative impacts on brain health. The inflammasome is a multiprotein complex that coordinates IL-1β and IL-18 production in response to tissue damage, cellular stress, and infection. Clinical evidence for inflammasome signaling in epileptogenesis is reviewed followed by a discussion of emerging strategies to modulate inflammasome activity in epilepsy.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612334","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}

{"title":"Prenatal drivers of microglia vulnerability in the adult","authors":"Erica Tagliatti,&nbsp;Matteo Bizzotto,&nbsp;Raffaella Morini,&nbsp;Fabia Filipello,&nbsp;Marco Rasile,&nbsp;Michela Matteoli","doi":"10.1111/imr.13418","DOIUrl":"10.1111/imr.13418","url":null,"abstract":"<p>Environmental insults during early development heavily affect brain trajectories. Among these, maternal infections, high-fat diet regimens, and sleep disturbances pose a significant risk for neurodevelopmental derangements in the offspring. Notably, scattered evidence is starting to emerge that also paternal lifestyle habits may impact the offspring development. Given their key role in controlling neurogenesis, synaptogenesis and shaping neuronal circuits, microglia represent the most likely suspects of mediating the detrimental effects of prenatal insults. For some of these environmental triggers, like maternal infections, ample literature evidence demonstrates the central role of microglia, also delineating the specific transcriptomic and proteomic profiles induced by these insults. In other contexts, the analysis of microglia is still in its infancy. Fostering these studies is needed to define microglia as potential therapeutic target in the frame of disorders consequent to maternal immune activation.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"327 1","pages":"100-110"},"PeriodicalIF":7.5,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.13418","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602548","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}

{"title":"Nucleic acid sensing in the central nervous system: Implications for neural circuit development, function, and degeneration","authors":"Jacob M. Stillman,&nbsp;Tsuyoshi Kiniwa,&nbsp;Dorothy P. Schafer","doi":"10.1111/imr.13420","DOIUrl":"10.1111/imr.13420","url":null,"abstract":"<div>\u0000 \u0000 <p>Nucleic acids are a critical trigger for the innate immune response to infection, wherein pathogen-derived RNA and DNA are sensed by nucleic acid sensing receptors. This subsequently drives the production of type I interferon and other inflammatory cytokines to combat infection. While the system is designed such that these receptors should specifically recognize pathogen-derived nucleic acids, it is now clear that self-derived RNA and DNA can also stimulate these receptors to cause aberrant inflammation and autoimmune disease. Intriguingly, similar pathways are now emerging in the central nervous system in neurons and glial cells. As in the periphery, these signaling pathways are active in neurons and glia to present the spread of pathogens in the CNS. They further appear to be active even under steady conditions to regulate neuronal development and function, and they can become activated aberrantly during disease to propagate neuroinflammation and neurodegeneration. Here, we review the emerging new roles for nucleic acid sensing mechanisms in the CNS and raise open questions that we are poised to explore in the future.</p>\u0000 </div>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"327 1","pages":"71-82"},"PeriodicalIF":7.5,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581417","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}