Immunological Reviews最新文献

{"title":"A comprehensive review of sensors of radiation-induced damage, radiation-induced proximal events, and cell death.","authors":"Saurabh Saini, Prajwal Gurung","doi":"10.1111/imr.13409","DOIUrl":"10.1111/imr.13409","url":null,"abstract":"<p><p>Radiation, a universal component of Earth's environment, is categorized into non-ionizing and ionizing forms. While non-ionizing radiation is relatively harmless, ionizing radiation possesses sufficient energy to ionize atoms and disrupt DNA, leading to cell damage, mutation, cancer, and cell death. The extensive use of radionuclides and ionizing radiation in nuclear technology and medical applications has sparked global concern for their capacity to cause acute and chronic illnesses. Ionizing radiation induces DNA damage either directly through strand breaks and base change or indirectly by generating reactive oxygen species (ROS) and reactive nitrogen species (RNS) via radiolysis of water. This damage triggers a complex cellular response involving recognition of DNA damage, cell cycle arrest, DNA repair mechanisms, release of pro-inflammatory cytokines, and cell death. This review focuses on the mechanisms of radiation-induced cellular damage, recognition of DNA damage and subsequent activation of repair processes, and the critical role of the innate immune response in resolution of the injury. Emphasis is placed on pattern recognition receptors (PRRs) and related receptors that detect damage-associated molecular patterns (DAMPs) and initiate downstream signaling pathways. Radiation-induced cell death pathways are discussed in detail. Understanding these processes is crucial for developing strategies to mitigate the harmful effects of radiation and improve therapeutic outcomes.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":" ","pages":"e13409"},"PeriodicalIF":7.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742653/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454231","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":"The Effector Functions of Antibodies","authors":"Marc Daëron","doi":"10.1111/imr.13428","DOIUrl":"10.1111/imr.13428","url":null,"abstract":"&lt;p&gt;“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.&lt;/p&gt;&lt;p&gt;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.&lt;/p&gt;&lt;p&gt;Why, therefore, put together another series of review articles on such well-known molecules? As stated in its title, this volume of &lt;i&gt;Immunological Reviews&lt;/i&gt; is focused on the &lt;i&gt;effector functions&lt;/i&gt; 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?&lt;/p&gt;&lt;p&gt;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":"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":"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}

{"title":"Life-threatening antibodies: The discovery of anaphylaxis","authors":"Marc Daëron,&nbsp;Birgitta Heyman,&nbsp;Anne Marie Moulin","doi":"10.1111/imr.13415","DOIUrl":"10.1111/imr.13415","url":null,"abstract":"<div>\u0000 \u0000 <p>It was at the turn of the 20th century, that immune serum was found both to save children dying from toxins of deadly pathogens, and to kill a dog within minutes following an injection of harmless doses of sea anemone toxins. This means that, before being formally identified in immune serum, antibodies were already known to be both protective and pathogenic. For this provocative finding, Charles Richet was awarded the 1913 Nobel Prize in Physiology or Medicine. Because, as its name said, anaphylaxis was understood as “the contrary of protection,” unique mechanisms were found to explain it. Because, as its name did not initially say but finally said, allergy was understood as a reaction “other” than immunity, its symptoms were explained by mechanisms similar to those that explained anaphylaxis. We examined here the intricate relationships between anaphylaxis, allergy and immunity. Progressively anaphylaxis became one among other pathological effects of an immune response, and allergy an inflammatory disease among others. Looking at antibodies back in the past enables us not only to learn where they come from, but also to follow trends that contributed to shape immunology, some of which may persist in today's immunological thinking and say something about the future.</p>\u0000 </div>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"328 1","pages":"24-38"},"PeriodicalIF":7.5,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566984","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":"CNS macrophage contributions to myelin health","authors":"Alana Hoffmann,&nbsp;Veronique E. Miron","doi":"10.1111/imr.13416","DOIUrl":"10.1111/imr.13416","url":null,"abstract":"<p>Myelin is the membrane surrounding neuronal axons in the central nervous system (CNS), produced by oligodendrocytes to provide insulation for electrical impulse conduction and trophic/metabolic support. CNS dysfunction occurs following poor development of myelin in infancy, myelin damage in neurological diseases, and impaired regeneration of myelin with disease progression in aging. The lack of approved therapies aimed at supporting myelin health highlights the critical need to identify the cellular and molecular influences on oligodendrocytes. CNS macrophages have been shown to influence the development, maintenance, damage and regeneration of myelin, revealing critical interactions with oligodendrocyte lineage cells. CNS macrophages are comprised of distinct populations, including CNS-resident microglia and cells associated with CNS border regions (the meninges, vasculature, and choroid plexus), in addition to macrophages derived from monocytes infiltrating from the blood. Importantly, the distinct contribution of these macrophage populations to oligodendrocyte lineage responses and myelin health are only just beginning to be uncovered, with the advent of new tools to specifically identify, track, and target macrophage subsets. Here, we summarize the current state of knowledge on the roles of CNS macrophages in myelin health, and recent developments in distinguishing the roles of macrophage populations in development, homeostasis, and disease.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"327 1","pages":"53-70"},"PeriodicalIF":7.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.13416","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556545","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":"The prototypical interferonopathy: Aicardi-Goutières syndrome from bedside to bench","authors":"Markus J. Hofer,&nbsp;Nicholson Modesti,&nbsp;Nicole G. Coufal,&nbsp;Qingde Wang,&nbsp;Sunetra Sase,&nbsp;Jonathan J. Miner,&nbsp;Adeline Vanderver,&nbsp;Mariko L. Bennett","doi":"10.1111/imr.13413","DOIUrl":"10.1111/imr.13413","url":null,"abstract":"<p>Aicardi-Goutières syndrome (AGS) is a progressive genetic encephalopathy caused by pathogenic mutations in genes controlling cellular anti-viral responses and nucleic acid metabolism. The mutations initiate autoinflammatory processes in the brain and systemically that are triggered by chronic overproduction of type I interferon (IFN), including IFN-alpha. Emerging disease-directed therapies aim to dampen autoinflammation and block cellular responses to IFN production, creating an urgent and unmet need to understand better which cells, compartments, and mechanisms underlying disease pathogenesis. In this review, we highlight existing pre-clinical models of AGS and our current understanding of how causative genetic mutations promote disease in AGS, to promote new model development and a continued focus on improving and directing future therapies.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"327 1","pages":"83-99"},"PeriodicalIF":7.5,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.13413","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542355","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}