Annual Review of Immunology

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  • Molecular Mechanisms Governing CD8 T Cell Differentiation and Checkpoint Inhibitor Response in Cancer
    CD8 T cells play a critical role in antitumor immunity. However, over time, they often become dysfunctional or exhausted and ultimately fail to control tumor growth. To effectively harness CD8 T cells for cancer immunotherapy, a detailed understanding …
  • Antigen Uptake in the Gut: An Underappreciated Piece to the Puzzle?
    The mammalian gut is a vast, diverse, and dynamic single-layer epithelial surface exposed to trillions of microbes, microbial products, and the diet. Underlying this epithelium lies the largest collection of immune cells in the body; these cells encoun…
  • Genetic Regulation of Cell Death: Insights from Autoinflammatory Diseases
    Metazoans have evolved innate antimicrobial defenses that promote cellular survival and proliferation. Countering the inevitable molecular mechanisms by which microbes sabotage these pathways, multicellular organisms rely on an alternative, perhaps mor…
  • Cellular and Molecular Mechanisms of Innate Memory Responses
    There has been an increasing effort to understand the memory responses of a complex interplay among innate, adaptive, and structural cells in peripheral organs and bone marrow. Trained immunity is coined as the de facto memory of innate immune cells an…
  • Protein Synthesis and Metabolism in T Cells
    T lymphocytes are essential for immune responses to pathogens and tumors. Their ability to rapidly clonally expand and differentiate to effector cells following infection, and then to curb effector function following infection clearance, is fundamental…
  • From Cytokines to Tuberculosis and Back: My Journey to Understanding the Immune Response to Infection
    I felt honored by the invitation to write this autobiography, although it was an arduous task to describe my journey through science: first bacterial adhesion, then cytokine function, and then immune responses in tuberculosis. Since only seven women ha…
  • Bidirectional Communication Between the Innate and Adaptive Immune Systems
    Effective bidirectional communication between the innate and adaptive immune systems is crucial for tissue homeostasis and protective immunity against infections. The innate immune system is responsible for the early sensing of and initial response to …
  • Humanized Mouse Systems to Study Viral Infection: A New Era in Immunology Research
    For decades, scientists have relied on traditional animal models to study viral infection and the immune response. However, these models have limitations, and the search for more accurate and reliable ways to study the human-pathogen interphase has led…
  • Barrier Integrity and Immunity: Exploring the Cutaneous Front Line in Health and Disease
    Immune responses are influenced by not only immune cells but also the tissue microenvironment where these cells reside. Recent advancements in understanding the underlying molecular mechanisms and structures of the epidermal tight junctions (TJs) and s…
  • Regulation of the cGAS-STING Pathway
    The cGAS-cGAMP-STING pathway is essential for immune defense against pathogens. Upon binding DNA, cGAS synthesizes cGAMP, which activates STING, leading to potent innate immune effector responses. However, lacking specific features to distinguish betwe…
  • Catch Bonds in Immunology
    Catch bonds are molecular bonds that last longer under force than slip bonds, which become shorter-lived under force. Although catch bonds were initially discovered in studies of leukocyte and bacterial adhesions two decades ago, they have since been f…
  • Central Nervous System Macrophages in Health and Disease
    The central nervous system (CNS) has a unique set of macrophages that seed the tissue early during embryonic development. Microglia reside in the parenchyma, and border-associated macrophages are present in border regions, including the meninges, periv…
  • The Interplay Between Innate Immunity and Nonimmune Cells in Lung Damage, Inflammation, and Repair
    As the site of gas exchange, the lung is critical for organismal survival. It is also subject to continual environmental insults inflicted by pathogens, particles, and toxins. Sometimes, these insults result in structural damage and the initiation of a…
  • The Integrated Pulmonary Immune Response to Pneumonia
    Pneumonia is an acute respiratory infection of the lower respiratory tract. The effectiveness of the host immune response determines the severity of infection, or whether pneumonia occurs at all. The lungs house both innate and adaptive immune systems,…
  • Engineering Mice to Study Human Immunity
    Humanized mice, which carry a human hematopoietic and immune system, have greatly advanced our understanding of human immune responses and immunological diseases. These mice are created via the transplantation of human hematopoietic stem and progenitor…
  • Macrophage Differentiation and Metabolic Adaptation in Mycobacterial Infections
    The adaptation of macrophages—the most common tissue-resident immune cells—to metabolic and microbial cues with high local variability is essential for the maintenance of organ integrity. In homeostasis, macrophages show largely predictable…
  • Neuroimmune Circuits in Allergic Diseases
    Communication between the nervous and immune systems is evolutionarily conserved. From primitive eukaryotes to higher mammals, neuroimmune communication utilizes multiple complex and complementary mechanisms to trigger effective but balanced responses …
  • Decoding Immunobiology Through Genetic Errors of Immunity
    Throughout biology, the pursuit of genotype-phenotype relationships has provided foundational knowledge upon which new concepts and hypotheses are built. Genetic perturbation, whether occurring naturally or in experimental settings, is the mainstay of …
  • Development and Functions of MAIT Cells
    Mucosal-associated invariant T (MAIT) cells are evolutionarily conserved T cells that recognize microbial metabolites. They are abundant in humans and conserved during mammalian evolution, which suggests that they have important nonredundant functions….
  • Using the Key Characteristics Framework to Unlock the Mysteries of Aryl Hydrocarbon Receptor–Mediated Effects on the Immune System
    Initially discovered for its role mediating the deleterious effects of environmental contaminants, the aryl hydrocarbon receptor (AHR) is now known to be a crucial regulator of the immune system. The expanding list of AHR ligands includes synthetic and…
  • Immune Regulation of Goblet Cell and Mucus Functions in Health and Disease
    The mucosal surfaces of the body are the most vulnerable points for infection because they are lined by single or multiple layers of very active epithelial cells. The main protector of these cells is the mucus system generated by the specialized goblet…
  • TNF/TNFR Superfamily Members in Costimulation of T Cell Responses—Revisited
    Prosurvival tumor necrosis factor receptor (TNFR) superfamily (TNFRSF) members on T cells, including 4-1BB, CD27, GITR, and OX40, support T cell accumulation during clonal expansion, contributing to T cell memory. During viral infection, tumor necrosis…
  • SARS-CoV-2: The Interplay Between Evolution and Host Immunity
    The persistence of SARS-CoV-2 infections at a global level reflects the repeated emergence of variant strains encoding unique constellations of mutations. These variants have been generated principally because of a dynamic host immune landscape, the co…
  • Tracing the Evolution of Human Immunity Through Ancient DNA
    Infections have imposed strong selection pressures throughout human evolution, making the study of natural selection’s effects on immunity genes highly complementary to disease-focused research. This review discusses how ancient DNA studies, which have…
  • T Cell Development and Responses in Human Immune System Mice
    Human Immune System (HIS) mice constructed with mature human immune cells or with human hematopoietic stem cells and thymic tissue have provided an important tool for human immunological research. In this article, we first review the different types of…
  • Kidney-Specific Interleukin-17 Responses During Infection and Injury
    The kidneys are life-sustaining organs that are vital to removing waste from our bodies. Because of their anatomic position and high blood flow, the kidneys are vulnerable to damage due to infections and autoinflammatory conditions. Even now, our knowl…
  • Priming and Maintenance of Adaptive Immunity in the Liver
    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 viru…
  • T Cell Exhaustion
    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 li…
  • The Immunobiology and Treatment of Food Allergy
    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 …
  • The Multifaceted Role of Tissue-Resident Memory T Cells
    Regionalized immune surveillance relies on the concerted efforts of diverse memory T cell populations. Of these, tissue-resident memory T (TRM) cells are strategically positioned in barrier tissues, where they enable efficient frontline defense against…
  • Immunology of Kidney Disease
    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…
  • Ontogeny and Function of Plasmacytoid Dendritic Cells
    Plasmacytoid dendritic cells (pDCs) represent a unique cell type within the innate immune system. Their defining property is the recognition of pathogen-derived nucleic acids through endosomal Toll-like receptors and the ensuing production of type I in…
  • TET Enzymes in the Immune System: From DNA Demethylation to Immunotherapy, Inflammation, and Cancer
    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-carboxylcyto…
  • Innate Immunity in Protection and Pathogenesis During Coronavirus Infections and COVID-19
    The COVID-19 pandemic was caused by the recently emerged β-coronavirus SARS-CoV-2. SARS-CoV-2 has had a catastrophic impact, resulting in nearly 7 million fatalities worldwide to date. The innate immune system is the first line of defense against …
  • The CD4 Versus CD8 T Cell Fate Decision: A Multiomics-Informed Perspective
    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…
  • Immune Responses in Controllers of HIV Infection
    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 t…
  • Beyond the Barrier: Unraveling the Mechanisms of Immunotherapy Resistance
    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 m…
  • Neuroimmune Interactions in the Intestine
    Recent advances have contributed to a mechanistic understanding of neuroimmune interactions in the intestine and revealed an essential role of this cross talk for gut homeostasis and modulation of inflammatory and infectious intestinal diseases. In thi…
  • Systemic Immune Modulation by Gastrointestinal Nematodes
    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 respons…
  • Poxvirus Immune Evasion
    Poxviruses have evolved a wide array of mechanisms to evade the immune response, and we provide an overview of the different immunomodulatory strategies. Poxviruses prevent the recognition of viral DNA that triggers the immune responses and inhibit sig…
  • Immune Activation in Alzheimer Disease
    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…
  • Microbial Metabolites and Gut Immunology
    The intestine is the largest peripheral lymphoid organ in animals, including humans, and interacts with a vast array of microorganisms called the gut microbiota. Comprehending the symbiotic relationship between the gut microbiota and our immune system …
  • Intraepithelial Lymphocytes of the Intestine
    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, …
  • Aire in Autoimmunity
    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 sin…
  • Multilayered Immunity by Tissue-Resident Lymphocytes in Cancer
    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-…
  • B Cell–Directed Therapy in Autoimmunity
    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 in…
  • Peeking Into the Black Box of T Cell Receptor Signaling
    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 an…
  • T Follicular Helper Cell Heterogeneity
    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 promo…
  • Circadian Rhythms in Anticancer Immunity: Mechanisms and Treatment Opportunities
    Circadian rhythms of approximately 24 h have emerged as important modulators of the immune system. These oscillations are important for mounting short-term, innate immune responses, but surprisingly also long-term, adaptive immune responses. Recent dat…
  • Neuroimmunology of the Lung
    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, re…
  • Effector-Triggered Immunity
    Annual Review of Immunology, Volume 41, Issue 1, Page 453-481, April 2023.
  • RNA Modification in the Immune System
    Annual Review of Immunology, Volume 41, Issue 1, Page 73-98, April 2023.
  • Host Recovery from Respiratory Viral Infection
    Annual Review of Immunology, Volume 41, Issue 1, Page 277-300, April 2023.
  • Origin and Heterogeneity of Tissue Myeloid Cells: A Focus on GMP-Derived Monocytes and Neutrophils
    Annual Review of Immunology, Volume 41, Issue 1, Page 375-404, April 2023.
  • IL-4 and IL-13: Regulators and Effectors of Wound Repair
    Annual Review of Immunology, Volume 41, Issue 1, Page 229-254, April 2023.
  • Structural Mechanisms of NLRP3 Inflammasome Assembly and Activation
    Annual Review of Immunology, Volume 41, Issue 1, Page 301-316, April 2023.
  • Biomaterials-Mediated Engineering of the Immune System
    Annual Review of Immunology, Volume 41, Issue 1, Page 153-179, April 2023.
  • Natural Killer Cells in the Human Uterine Mucosa
    Annual Review of Immunology, Volume 41, Issue 1, Page 127-151, April 2023.
  • Systems Immunology Approaches to Metabolism
    Annual Review of Immunology, Volume 41, Issue 1, Page 317-342, April 2023.
  • The Immunological Conundrum of Endogenous Retroelements
    Annual Review of Immunology, Volume 41, Issue 1, Page 99-125, April 2023.
  • Designing Cancer Immunotherapies That Engage T Cells and NK Cells
    Annual Review of Immunology, Volume 41, Issue 1, Page 17-38, April 2023.
  • Extremely Differentiated T Cell Subsets Contribute to Tissue Deterioration During Aging
    Annual Review of Immunology, Volume 41, Issue 1, Page 181-205, April 2023.
  • Not Dead Yet
    Annual Review of Immunology, Volume 41, Issue 1, Page 1-15, April 2023.
  • Systemic Lupus Erythematosus Pathogenesis: Interferon and Beyond
    Annual Review of Immunology, Volume 41, Issue 1, Page 533-560, April 2023.
  • TGF-β Regulation of T Cells
    Annual Review of Immunology, Volume 41, Issue 1, Page 483-512, April 2023.
  • Immune-Epithelial Cross Talk in Regeneration and Repair
    Annual Review of Immunology, Volume 41, Issue 1, Page 207-228, April 2023.
  • Immune Mechanisms in Inflammatory Anemia
    Annual Review of Immunology, Volume 41, Issue 1, Page 405-429, April 2023.
  • IgE, IgE Receptors and Anti-IgE Biologics: Protein Structures and Mechanisms of Action
    Annual Review of Immunology, Volume 41, Issue 1, Page 255-275, April 2023.
  • Modeling T Cell Fate
    Annual Review of Immunology, Volume 41, Issue 1, Page 513-532, April 2023.
  • Complement in the Brain: Contributions to Neuroprotection, Neuronal Plasticity, and Neuroinflammation
    Annual Review of Immunology, Volume 41, Issue 1, Page 431-452, April 2023.
  • Reconciling Mouse and Human Immunology at the Altar of Genetics
    Annual Review of Immunology, Volume 41, Issue 1, Page 39-71, April 2023.
  • Interfering with Interferons: A Critical Mechanism for Critical COVID-19 Pneumonia
    Annual Review of Immunology, Volume 41, Issue 1, Page 561-585, April 2023.
  • T Cell Responses to SARS-CoV-2
    Annual Review of Immunology, Volume 41, Issue 1, Page 343-373, April 2023.
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