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Immune Activation in Alzheimer Disease Annu. Rev. Immunol. (IF 29.7) Pub Date : 2024-03-01 Arnaud Mary, Renzo Mancuso, Michael T. Heneka
Alzheimer disease (AD) is the most common neurodegenerative disease, and with no efficient curative treatment available, its medical, social, and economic burdens are expected to dramatically increase. AD is historically characterized by amyloid β (Aβ) plaques and tau neurofibrillary tangles, but over the last 25 years chronic immune activation has been identified as an important factor contributing
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Multilayered Immunity by Tissue-Resident Lymphocytes in Cancer Annu. Rev. Immunol. (IF 29.7) Pub Date : 2024-03-01 Ming O. Li, Jing Zhang, Zijian Xu, Xian Zhang, Peng Li, Andrew E. Cornish
Lymphocytes spanning the entire innate-adaptive spectrum can stably reside in tissues and constitute an integral component of the local defense network against immunological challenges. In tight interactions with the epithelium and endothelium, tissue-resident lymphocytes sense antigens and alarmins elicited by infectious microbes and abiotic stresses at barrier sites and mount effector responses to
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Beyond the Barrier: Unraveling the Mechanisms of Immunotherapy Resistance Annu. Rev. Immunol. (IF 29.7) Pub Date : 2024-02-21 Hannah N. Bell, Weiping Zou
Immune checkpoint blockade (ICB) induces a remarkable and durable response in a subset of cancer patients. However, most patients exhibit either primary or acquired resistance to ICB. This resistance arises from a complex interplay of diverse dynamic mechanisms within the tumor microenvironment (TME). These mechanisms include genetic, epigenetic, and metabolic alterations that prevent T cell trafficking
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Priming and Maintenance of Adaptive Immunity in the Liver Annu. Rev. Immunol. (IF 29.7) Pub Date : 2024-02-16 Keigo Kawashima, Francesco Andreata, Cristian Gabriel Beccaria, Matteo Iannacone
The liver's unique characteristics have a profound impact on the priming and maintenance of adaptive immunity. This review delves into the cellular circuits that regulate adaptive immune responses in the liver, with a specific focus on hepatitis B virus infection as an illustrative example. A key aspect highlighted is the liver's specialized role in priming CD8+ T cells, leading to a distinct state
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Aire in Autoimmunity Annu. Rev. Immunol. (IF 29.7) Pub Date : 2024-02-16 Corey N. Miller, Michael R. Waterfield, James M. Gardner, Mark S. Anderson
The role of the autoimmune regulator (Aire) in central immune tolerance and thymic self-representation was first described more than 20 years ago, but fascinating new insights into its biology continue to emerge, particularly in the era of advanced single-cell genomics. We briefly describe the role of human genetics in the discovery of Aire, as well as insights into its function gained from genotype–phenotype
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The Immunobiology and Treatment of Food Allergy Annu. Rev. Immunol. (IF 29.7) Pub Date : 2024-02-16 Suzanne Barshow, Jyothi Tirumalasetty, Vanitha Sampath, Xiaoying Zhou, Hana Seastedt, Jackson Schuetz, Kari Nadeau
IgE-mediated food allergy (IgE-FA) occurs due to a breakdown in immune tolerance that leads to a detrimental type 2 helper T cell (TH2) adaptive immune response. While the processes governing this loss of tolerance are incompletely understood, several host-related and environmental factors impacting the risk of IgE-FA development have been identified. Mounting evidence supports the role of an impaired
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TET Enzymes in the Immune System: From DNA Demethylation to Immunotherapy, Inflammation, and Cancer Annu. Rev. Immunol. (IF 29.7) Pub Date : 2024-02-16 Isaac F. López-Moyado, Myunggon Ko, Patrick G. Hogan, Anjana Rao
Ten-eleven translocation (TET) proteins are iron-dependent and α-ketoglutarate-dependent dioxygenases that sequentially oxidize the methyl group of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). All three epigenetic modifications are intermediates in DNA demethylation. TET proteins are recruited by transcription factors and by RNA polymerase
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Intraepithelial Lymphocytes of the Intestine Annu. Rev. Immunol. (IF 29.7) Pub Date : 2024-01-26 Ainsley Lockhart, Daniel Mucida, Angelina M. Bilate
The intestinal epithelium, which segregates the highly stimulatory lumen from the underlying tissue, harbors one of the largest lymphocyte populations in the body, intestinal intraepithelial lymphocytes (IELs). IELs must balance tolerance, resistance, and tissue protection to maintain epithelial homeostasis and barrier integrity. This review discusses the ontogeny, environmental imprinting, T cell
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Systemic Immune Modulation by Gastrointestinal Nematodes Annu. Rev. Immunol. (IF 29.7) Pub Date : 2024-01-26 Darshan N. Kasal, Lindsey Warner, Astra Bryant, Elia Tait-Wojno, Jakob von Moltke
Gastrointestinal nematode (GIN) infection has applied significant evolutionary pressure to the mammalian immune system and remains a global economic and human health burden. Upon infection, type 2 immune sentinels activate a common antihelminth response that mobilizes and remodels the intestinal tissue for effector function; however, there is growing appreciation of the impact GIN infection also has
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The CD4 Versus CD8 T Cell Fate Decision: A Multiomics-Informed Perspective Annu. Rev. Immunol. (IF 29.7) Pub Date : 2024-01-25 Zoë Steier, Esther Jeong Yoon Kim, Dominik A. Aylard, Ellen A. Robey
The choice of developing thymocytes to become CD8+ cytotoxic or CD4+ helper T cells has been intensely studied, but many of the underlying mechanisms remain to be elucidated. Recent multiomics approaches have provided much higher resolution analysis of gene expression in developing thymocytes than was previously achievable, thereby offering a fresh perspective on this question. Focusing on our recent
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Immunology of Kidney Disease Annu. Rev. Immunol. (IF 29.7) Pub Date : 2024-01-12 Orestes Foresto-Neto, Luísa Menezes-Silva, Jefferson Antônio Leite, Magaiver Andrade-Silva, Niels Olsen Saraiva Câmara
The immune system and the kidneys are closely related. Immune components mediate acute kidney disease and are crucial to the progression of chronic kidney disease. Beyond its pathogenic functions, the immune system supports immunological homeostasis in healthy kidneys. The kidneys help maintain immune equilibrium by removing metabolic waste products and toxins, thereby limiting local and systemic inflammation
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T Cell Exhaustion Annu. Rev. Immunol. (IF 29.7) Pub Date : 2024-01-02 Andrew Baessler, Dario A.A. Vignali
T cell responses must be balanced to ensure adequate protection against malignant transformation and an array of pathogens while also limiting damage to healthy cells and preventing autoimmunity. T cell exhaustion serves as a regulatory mechanism to limit the activity and effector function of T cells undergoing chronic antigen stimulation. Exhausted T cells exhibit poor proliferative potential; high
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T Follicular Helper Cell Heterogeneity Annu. Rev. Immunol. (IF 29.7) Pub Date : 2023-12-07 Wenzhi Song, Joe Craft
T follicular helper (Tfh) cells specialize in helping B cells and are therefore critical contributors to the generation of humoral immunity. Tfh cells aid immunoglobulin class-switch recombination and support the germinal center response, thereby promoting immunoglobulin affinity maturation and the generation of humoral immune memory. Although their primary function is to promote B cell responses,
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B Cell–Directed Therapy in Autoimmunity Annu. Rev. Immunol. (IF 29.7) Pub Date : 2023-11-28 Ilana Abeles, Chris Palma, Nida Meednu, Aimee S. Payne, R. John Looney, Jennifer H. Anolik
Autoimmune diseases with B cell–directed therapeutics approved by the US Food and Drug Administration are surprisingly diverse in clinical manifestations and pathophysiology. In this review, we focus on recent clinical and mechanistic insights into the efficacy of B cell depletion in these diverse autoimmune disorders, the rapidly expanding armamentarium of approved agents, and future approaches. The
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Neuroimmune Interactions in the Lung Annu. Rev. Immunol. (IF 29.7) Pub Date : 2023-11-21 Rossana Azzoni, Olaf Perdijk, Nicola L. Harris, Benjamin J. Marsland
Barrier tissues are highly innervated by sensory and autonomic nerves that are positioned in close proximity to both stromal and immune cell populations. Together with a growing awareness of the far-reaching consequences of neuroimmune interactions, recent studies have uncovered key mechanisms through which they contribute to organ homeostasis and immunity. It has also become clear that dysregulation
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Kidney-Specific Interleukin-17 Responses During Infection and Injury Annu. Rev. Immunol. (IF 29.7) Pub Date : 2023-10-31 Doureradjou Peroumal, Partha S. Biswas
The kidneys are life-sustaining organs that are vital to removing waste from our body. Because of their anatomic position and high blood flow, the kidneys are vulnerable to damage due to infections and autoinflammatory conditions. Even now, our knowledge of immune responses in the kidney is surprisingly rudimentary. Studying kidney-specific immune events are challenging because of the poor regenerative
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Immune Responses in Controllers of HIV Infection Annu. Rev. Immunol. (IF 29.7) Pub Date : 2023-10-12 Abena K. Kwaa, Joel N. Blankson
Elite controllers are a heterogeneous group of people living with HIV who control viral replication without antiretroviral therapy. There is substantial evidence that at least some elite controllers are infected with replication-competent virus, thus they may serve as a model of a functional cure of HIV. The mechanisms responsible for virologic control have been actively studied. The most objective
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Peeking Into the Black Box of T Cell Receptor Signaling Annu. Rev. Immunol. (IF 29.7) Pub Date : 2023-10-03 Arthur Weiss
I have spent more than the last 40 years at the University of California, San Francisco (UCSF), studying T cell receptor (TCR) signaling. I was blessed with supportive mentors, an exceptionally talented group of trainees, and wonderful collaborators and colleagues during my journey who have enabled me to make significant contributions to our understanding of how the TCR initiates signaling. TCR signaling
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Modeling T Cell Fate Annu. Rev. Immunol. (IF 29.7) Pub Date : 2023-04-26 Rob J. De Boer, Andrew J. Yates
Many of the pathways that underlie the diversification of naive T cells into effector and memory subsets, and the maintenance of these populations, remain controversial. In recent years a variety of experimental tools have been developed that allow us to follow the fates of cells and their descendants. In this review we describe how mathematical models provide a natural language for describing the
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Interfering with Interferons: A Critical Mechanism for Critical COVID-19 Pneumonia Annu. Rev. Immunol. (IF 29.7) Pub Date : 2023-04-26 Helen C. Su, Huie Jing, Yu Zhang, Jean-Laurent Casanova
Infection with SARS-CoV-2 results in clinical outcomes ranging from silent or benign infection in most individuals to critical pneumonia and death in a few. Genetic studies in patients have established that critical cases can result from inborn errors of TLR3- or TLR7-dependent type I interferon immunity, or from preexisting autoantibodies neutralizing primarily IFN-α and/or IFN-ω. These findings are
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Origin and Heterogeneity of Tissue Myeloid Cells: A Focus on GMP-Derived Monocytes and Neutrophils Annu. Rev. Immunol. (IF 29.7) Pub Date : 2023-04-26 Lai Guan Ng, Zhaoyuan Liu, Immanuel Kwok, Florent Ginhoux
Myeloid cells are a significant proportion of leukocytes within tissues, comprising granulocytes, monocytes, dendritic cells, and macrophages. With the identification of various myeloid cells that perform separate but complementary functions during homeostasis and disease, our understanding of tissue myeloid cells has evolved significantly. Exciting findings from transcriptomics profiling and fate-mapping
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Not Dead Yet Annu. Rev. Immunol. (IF 29.7) Pub Date : 2023-04-26 Betty Diamond
I have been a scientific grasshopper throughout my career, moving from question to question within the domain of lupus. This has proven to be immensely gratifying. Scientific exploration is endlessly fascinating, and succeeding in studies you care about with colleagues and trainees leads to strong and lasting bonds. Science isn't easy; being a woman in science presents challenges, but the drive to
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RNA Modification in the Immune System Annu. Rev. Immunol. (IF 29.7) Pub Date : 2023-04-26 Dali Han, Meng Michelle Xu
Characterization of RNA modifications has identified their distribution features and molecular functions. Dynamic changes in RNA modification on various forms of RNA are essential for the development and function of the immune system. In this review, we discuss the value of innovative RNA modification profiling technologies to uncover the function of these diverse, dynamic RNA modifications in various
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Extremely Differentiated T Cell Subsets Contribute to Tissue Deterioration During Aging Annu. Rev. Immunol. (IF 29.7) Pub Date : 2023-04-26 Gonzalo Soto-Heredero, Manuel M. Gómez de las Heras, J. Ignacio Escrig-Larena, María Mittelbrunn
There is a dramatic remodeling of the T cell compartment during aging. The most notorious changes are the reduction of the naive T cell pool and the accumulation of memory-like T cells. Memory-like T cells in older people acquire a phenotype of terminally differentiated cells, lose the expression of costimulatory molecules, and acquire properties of senescent cells. In this review, we focus on the
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Systems Immunology Approaches to Metabolism Annu. Rev. Immunol. (IF 29.7) Pub Date : 2023-04-26 Denis A. Mogilenko, Alexey Sergushichev, Maxim N. Artyomov
Over the last decade, immunometabolism has emerged as a novel interdisciplinary field of research and yielded significant fundamental insights into the regulation of immune responses. Multiple classical approaches to interrogate immunometabolism, including bulk metabolic profiling and analysis of metabolic regulator expression, paved the way to appreciating the physiological complexity of immunometabolic
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Systemic Lupus Erythematosus Pathogenesis: Interferon and Beyond Annu. Rev. Immunol. (IF 29.7) Pub Date : 2023-02-28 Simone Caielli, Zurong Wan, Virginia Pascual
Autoreactive B cells and interferons are central players in systemic lupus erythematosus (SLE) pathogenesis. The partial success of drugs targeting these pathways, however, supports heterogeneity in upstream mechanisms contributing to disease pathogenesis. In this review, we focus on recent insights from genetic and immune monitoring studies of patients that are refining our understanding of these
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Structural Mechanisms of NLRP3 Inflammasome Assembly and Activation Annu. Rev. Immunol. (IF 29.7) Pub Date : 2023-02-08 Jianing Fu, Hao Wu
As an important sensor in the innate immune system, NLRP3 detects exogenous pathogenic invasions and endogenous cellular damage and responds by forming the NLRP3 inflammasome, a supramolecular complex that activates caspase-1. The three major components of the NLRP3 inflammasome are NLRP3, which captures the danger signals and recruits downstream molecules; caspase-1, which elicits maturation of the
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T Cell Responses to SARS-CoV-2 Annu. Rev. Immunol. (IF 29.7) Pub Date : 2023-02-08 Alessandro Sette, John Sidney, Shane Crotty
A large body of evidence generated in the last two and a half years addresses the roles of T cells in SARS-CoV-2 infection and following vaccination. Infection or vaccination induces multi-epitope CD4 and CD8 T cell responses with polyfunctionality. Early T cell responses have been associated with mild COVID-19 outcomes. In concert with animal model data, these results suggest that while antibody responses
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TGF-β Regulation of T Cells Annu. Rev. Immunol. (IF 29.7) Pub Date : 2023-02-08 WanJun Chen
Transforming growth factor β (TGF-β) is a key cytokine regulating the development, activation, proliferation, differentiation, and death of T cells. In CD4+ T cells, TGF-β maintains the quiescence and controls the activation of naive T cells. While inhibiting the differentiation and function of Th1 and Th2 cells, TGF-β promotes the differentiation of Th17 and Th9 cells. TGF-β is required for the induction
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Effector-Triggered Immunity Annu. Rev. Immunol. (IF 29.7) Pub Date : 2023-02-08 Brenna C. Remick, Moritz M. Gaidt, Russell E. Vance
The innate immune system detects pathogens via germline-encoded receptors that bind to conserved pathogen ligands called pathogen-associated molecular patterns (PAMPs). Here we consider an additional strategy of pathogen sensing called effector-triggered immunity (ETI). ETI involves detection of pathogen-encoded virulence factors, also called effectors. Pathogens produce effectors to manipulate hosts
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Immune Mechanisms in Inflammatory Anemia Annu. Rev. Immunol. (IF 29.7) Pub Date : 2023-02-08 Susan P. Canny, Susana L. Orozco, Natalie K. Thulin, Jessica A. Hamerman
Maintaining the correct number of healthy red blood cells (RBCs) is critical for proper oxygenation of tissues throughout the body. Therefore, RBC homeostasis is a tightly controlled balance between RBC production and RBC clearance, through the processes of erythropoiesis and macrophage hemophagocytosis, respectively. However, during the inflammation associated with infectious, autoimmune, or inflammatory
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Complement in the Brain: Contributions to Neuroprotection, Neuronal Plasticity, and Neuroinflammation Annu. Rev. Immunol. (IF 29.7) Pub Date : 2023-02-08 Suzanne S. Bohlson, Andrea J. Tenner
The complement system is an ancient collection of proteolytic cascades with well-described roles in regulation of innate and adaptive immunity. With the convergence of a revolution in complement-directed clinical therapeutics, the discovery of specific complement-associated targetable pathways in the central nervous system, and the development of integrated multi-omic technologies that have all emerged
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IL-4 and IL-13: Regulators and Effectors of Wound Repair Annu. Rev. Immunol. (IF 29.7) Pub Date : 2023-02-04 Judith E. Allen
Type 2 immunity mediates protective responses to helminths and pathological responses to allergens, but it also has broad roles in the maintenance of tissue integrity, including wound repair. Type 2 cytokines are known to promote fibrosis, an overzealous repair response, but their contribution to healthy wound repair is less well understood. This review discusses the evidence that the canonical type
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IgE, IgE Receptors and Anti-IgE Biologics: Protein Structures and Mechanisms of Action Annu. Rev. Immunol. (IF 29.7) Pub Date : 2023-02-04 J.M. McDonnell, B. Dhaliwal, B.J. Sutton, H.J. Gould
The evolution of IgE in mammals added an extra layer of immune protection at body surfaces to provide a rapid and local response against antigens from the environment. The IgE immune response employs potent expulsive and inflammatory forces against local antigen provocation, at the risk of damaging host tissues and causing allergic disease. Two well-known IgE receptors, the high-affinity FcεRI and
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Host Recovery from Respiratory Viral Infection Annu. Rev. Immunol. (IF 29.7) Pub Date : 2023-01-30 Xiaoqin Wei, Harish Narasimhan, Bibo Zhu, Jie Sun
Emerging and re-emerging respiratory viral infections pose a tremendous threat to human society, as exemplified by the ongoing COVID-19 pandemic. Upon viral invasion of the respiratory tract, the host initiates coordinated innate and adaptive immune responses to defend against the virus and to promote repair of the damaged tissue. However, dysregulated host immunity can also cause acute morbidity,
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Biomaterials-Mediated Engineering of the Immune System Annu. Rev. Immunol. (IF 29.7) Pub Date : 2023-01-25 Coralie Backlund, Sasan Jalili-Firoozinezhad, Byungji Kim, Darrell J. Irvine
Modulation of the immune system is an important therapeutic strategy in a wide range of diseases, and is fundamental to the development of vaccines. However, optimally safe and effective immunotherapy requires precision in the delivery of stimulatory cues to the right cells at the right place and time, to avoid toxic overstimulation in healthy tissues or incorrect programming of the immune response
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Immune-Epithelial Cross Talk in Regeneration and Repair Annu. Rev. Immunol. (IF 29.7) Pub Date : 2023-01-25 Laure Guenin-Mace, Piotr Konieczny, Shruti Naik
The epithelial tissues that line our body, such as the skin and gut, have remarkable regenerative prowess and continually renew throughout our lifetimes. Owing to their barrier function, these tissues have also evolved sophisticated repair mechanisms to swiftly heal and limit the penetration of harmful agents following injury. Researchers now appreciate that epithelial regeneration and repair are not
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The Immunological Conundrum of Endogenous Retroelements Annu. Rev. Immunol. (IF 29.7) Pub Date : 2023-01-11 George Kassiotis
Our defenses against infection rely on the ability of the immune system to distinguish invading pathogens from self. This task is exceptionally challenging, if not seemingly impossible, in the case of retroviruses that have integrated almost seamlessly into the host. This review examines the limits of innate and adaptive immune responses elicited by endogenous retroviruses and other retroelements,
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Natural Killer Cells in the Human Uterine Mucosa Annu. Rev. Immunol. (IF 29.7) Pub Date : 2023-01-11 Victoria Male, Ashley Moffett
The presence of granulated lymphocytes in the human uterine mucosa, known as decidua during pregnancy, or endometrium otherwise, was first noted in the nineteenth century, but it was not until 1990 that these cells were identified as a type of natural killer (NK) cell. From the outset, uterine NK (uNK) cells were found to be less cytotoxic than their circulating counterparts, peripheral NK (pNK) cells
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Reconciling Mouse and Human Immunology at the Altar of Genetics Annu. Rev. Immunol. (IF 29.7) Pub Date : 2022-12-16 Philippe Gros, Jean-Laurent Casanova
Immunity to infection has been extensively studied in humans and mice bearing naturally occurring or experimentally introduced germline mutations. Mouse studies are sometimes neglected by human immunologists, on the basis that mice are not humans and the infections studied are experimental and not natural. Conversely, human studies are sometimes neglected by mouse immunologists, on the basis of the
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Designing Cancer Immunotherapies That Engage T Cells and NK Cells Annu. Rev. Immunol. (IF 29.7) Pub Date : 2022-11-29 Oleksandr Kyrysyuk, Kai W. Wucherpfennig
T cells and natural killer (NK) cells have complementary roles in tumor immunity, and dual T cell and NK cell attack thus offers opportunities to deepen the impact of immunotherapy. Recent work has also shown that NK cells play an important role in recruiting dendritic cells to tumors and thus enhance induction of CD8 T cell responses, while IL-2 secreted by T cells activates NK cells. Targeting of
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Exposing T Cell Secrets Inside and Outside the Thymus Annu. Rev. Immunol. (IF 29.7) Pub Date : 2022-04-26 Pamela J. Fink
I've had serious misgivings about writing this article, because from living the experience day by day, it's hard to believe my accomplishments merit the attention. To skirt this roadblock, I forced myself to pretend I was in a conversation with my trainees, trying to distill the central driving forces of my career in science. The below chronicles my evolution from would-be astronaut/ballerina to budding
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Tissue Immunity in the Bladder Annu. Rev. Immunol. (IF 29.7) Pub Date : 2022-04-26 Georgina S. Bowyer, Kevin W. Loudon, Ondrej Suchanek, Menna R. Clatworthy
The bladder is a major component of the urinary tract, an organ system that expels metabolic waste and excess water, which necessitates proximity to the external environment and its pathogens. It also houses a commensal microbiome. Therefore, its tissue immunity must resist pathogen invasion while maintaining tolerance to commensals. Bacterial infection of the bladder is common, with half of women
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Emerging Paradigms in Type 2 Immunity Annu. Rev. Immunol. (IF 29.7) Pub Date : 2022-04-26 Hamida Hammad, Nincy Debeuf, Helena Aegerter, Andrew S. Brown, Bart N. Lambrecht
A principal purpose of type 2 immunity was thought to be defense against large parasites, but it also functions in the restoration of homeostasis, such as toxin clearance following snake bites. In other cases, like allergy, the type 2 T helper (Th2) cytokines and cells present in the environment are detrimental and cause diseases. In recent years, the recognition of cell heterogeneity within Th2-associated
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Functional Hallmarks of Healthy Macrophage Responses: Their Regulatory Basis and Disease Relevance Annu. Rev. Immunol. (IF 29.7) Pub Date : 2022-04-26 Katherine M. Sheu, Alexander Hoffmann
Macrophages are first responders for the immune system. In this role, they have both effector functions for neutralizing pathogens and sentinel functions for alerting other immune cells of diverse pathologic threats, thereby initiating and coordinating a multipronged immune response. Macrophages are distributed throughout the body—they circulate in the blood, line the mucosal membranes, reside within
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Instructive Cues of Thymic T Cell Selection Annu. Rev. Immunol. (IF 29.7) Pub Date : 2022-04-26 Magali Irla
A high diversity of αβ T cell receptors (TCRs), capable of recognizing virtually any pathogen but also self-antigens, is generated during T cell development in the thymus. Nevertheless, a strict developmental program supports the selection of a self-tolerant T cell repertoire capable of responding to foreign antigens. The steps of T cell selection are controlled by cortical and medullary stromal niches
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Resistance Mechanisms to Anti-PD Cancer Immunotherapy Annu. Rev. Immunol. (IF 29.7) Pub Date : 2022-04-26 Matthew D. Vesely, Tianxiang Zhang, Lieping Chen
The transformative success of antibodies targeting the PD-1 (programmed death 1)/B7-H1 (B7 homolog 1) pathway (anti-PD therapy) has revolutionized cancer treatment. However, only a fraction of patients with solid tumors and some hematopoietic malignancies respond to anti-PD therapy, and the reason for failure in other patients is less known. By dissecting the mechanisms underlying this resistance,
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Innate Sensors Trigger Regulated Cell Death to Combat Intracellular Infection Annu. Rev. Immunol. (IF 29.7) Pub Date : 2022-02-09 Kengo Nozaki, Lupeng Li, Edward A. Miao
Intracellular pathogens pose a significant threat to animals. In defense, innate immune sensors attempt to detect these pathogens using pattern recognition receptors that either directly detect microbial molecules or indirectly detect their pathogenic activity. These sensors trigger different forms of regulated cell death, including pyroptosis, apoptosis, and necroptosis, which eliminate the infected
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Distinct Cellular Tropism and Immune Responses to Alphavirus Infection Annu. Rev. Immunol. (IF 29.7) Pub Date : 2022-02-08 Natasha M. Kafai, Michael S. Diamond, Julie M. Fox
Alphaviruses are emerging and reemerging viruses that cause disease syndromes ranging from incapacitating arthritis to potentially fatal encephalitis. While infection by arthritogenic and encephalitic alphaviruses results in distinct clinical manifestations, both virus groups induce robust innate and adaptive immune responses. However, differences in cellular tropism, type I interferon induction, immune
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Spatiotemporal Adaptations of Macrophage and Dendritic Cell Development and Function Annu. Rev. Immunol. (IF 29.7) Pub Date : 2022-02-07 Antoine Roquilly, Justine D. Mintern, Jose A. Villadangos
Macrophages and conventional dendritic cells (cDCs) are distributed throughout the body, maintaining tissue homeostasis and tolerance to self and orchestrating innate and adaptive immunity against infection and cancer. As they complement each other, it is important to understand how they cooperate and the mechanisms that integrate their functions. Both are exposed to commensal microbes, pathogens,
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The Tuberculous Granuloma and Preexisting Immunity Annu. Rev. Immunol. (IF 29.7) Pub Date : 2022-02-07 Sara B. Cohen, Benjamin H. Gern, Kevin B. Urdahl
Pulmonary granulomas are widely considered the epicenters of the immune response to Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB). Recent animal studies have revealed factors that either promote or restrict TB immunity within granulomas. These models, however, typically ignore the impact of preexisting immunity on cellular organization and function, an important consideration
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Gene Regulatory Circuits in Innate and Adaptive Immune Cells Annu. Rev. Immunol. (IF 29.7) Pub Date : 2022-02-04 Ankita Saini, Hazem E. Ghoneim, Chan-Wang Jerry Lio, Patrick L. Collins, Eugene M. Oltz
Cell identity and function largely rely on the programming of transcriptomes during development and differentiation. Signature gene expression programs are orchestrated by regulatory circuits consisting of cis-acting promoters and enhancers, which respond to a plethora of cues via the action of transcription factors. In turn, transcription factors direct epigenetic modifications to revise chromatin
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Germinal Centers Annu. Rev. Immunol. (IF 29.7) Pub Date : 2022-02-03 Gabriel D. Victora, Michel C. Nussenzweig
Germinal centers (GCs) are microanatomical sites of B cell clonal expansion and antibody affinity maturation. Therein, B cells undergo the Darwinian process of somatic diversification and affinity-driven selection of immunoglobulins that produces the high-affinity antibodies essential for effective humoral immunity. Here, we review recent developments in the field of GC biology, primarily as it pertains
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Human Antibodies for Viral Infections Annu. Rev. Immunol. (IF 29.7) Pub Date : 2022-02-03 James E. Crowe
Antibodies have been used to prevent or treat viral infections since the nineteenth century, but the full potential to use passive immunization for infectious diseases has yet to be realized. The advent of efficient methods for isolating broad and potently neutralizing human monoclonal antibodies is enabling us to develop antibodies with unprecedented activities. The discovery of IgG Fc region modifications
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T Cell Responses to the Microbiota Annu. Rev. Immunol. (IF 29.7) Pub Date : 2022-02-03 Ivaylo I. Ivanov, Timur Tuganbaev, Ashwin N. Skelly, Kenya Honda
The immune system employs recognition tools to communicate with its microbial evolutionary partner. Among all the methods of microbial perception, T cells enable the widest spectrum of microbial recognition resolution, ranging from the crudest detection of whole groups of microbes to the finest detection of specific antigens. The application of this recognition capability to the crucial task of combatting
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IL-6 Revisited: From Rheumatoid Arthritis to CAR T Cell Therapy and COVID-19 Annu. Rev. Immunol. (IF 29.7) Pub Date : 2022-02-03 Tadamitsu Kishimoto, Sujin Kang
The diverse biological activity of interleukin-6 (IL-6) contributes to the maintenance of homeostasis. Emergent infection or tissue injury induces rapid production of IL-6 and activates host defense through augmentation of acute-phase proteins and immune responses. However, excessive IL-6 production and uncontrolled IL-6 receptor signaling are critical to pathogenesis. Over the years, therapeutic agents
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Evolutionary Landscapes of Host-Virus Arms Races Annu. Rev. Immunol. (IF 29.7) Pub Date : 2022-01-26 Jeannette L. Tenthorey, Michael Emerman, Harmit S. Malik
Vertebrate immune systems suppress viral infection using both innate restriction factors and adaptive immunity. Viruses mutate to escape these defenses, driving hosts to counterevolve to regain fitness. This cycle recurs repeatedly, resulting in an evolutionary arms race whose outcome depends on the pace and likelihood of adaptation by host and viral genes. Although viruses evolve faster than their
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Inflammatory Caspases: Toward a Unified Model for Caspase Activation by Inflammasomes Annu. Rev. Immunol. (IF 29.7) Pub Date : 2022-01-26 Connie Ross, Amy H. Chan, Jessica B. von Pein, Madhavi P. Maddugoda, Dave Boucher, Kate Schroder
Inflammasomes are inflammatory signaling complexes that provide molecular platforms to activate the protease function of inflammatory caspases. Caspases-1, -4, -5, and -11 are inflammatory caspases activated by inflammasomes to drive lytic cell death and inflammatory mediator production, thereby activating host-protective and pathological immune responses. Here, we comprehensively review the mechanisms
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Molecular Mechanisms of Multimeric Assembly of IgM and IgA Annu. Rev. Immunol. (IF 29.7) Pub Date : 2022-01-21 Marissa L. Matsumoto
As central effectors of the adaptive immune response, immunoglobulins, or antibodies, provide essential protection from pathogens through their ability to recognize foreign antigens, aid in neutralization, and facilitate elimination from the host. Mammalian immunoglobulins can be classified into five isotypes—IgA, IgD, IgE, IgG, and IgM—each with distinct roles in mediating various aspects of the immune
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Tissue-Resident Immune Cells in Humans Annu. Rev. Immunol. (IF 29.7) Pub Date : 2022-01-19 Joshua I. Gray, Donna L. Farber
Tissue-resident immune cells span both myeloid and lymphoid cell lineages, have been found in multiple human tissues, and play integral roles at all stages of the immune response, from maintaining homeostasis to responding to infectious challenges to resolution of inflammation to tissue repair. In humans, studying immune cells and responses in tissues is challenging, although recent advances in sampling