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This Review discusses the evidence for pre-existing cross-reactive immune responses to SARS-CoV-2, which are mainly due to infections with common cold coronaviruses, and how such cross-reactivity affects adaptive immune responses. Furthermore, it explores cross-reactivity in the context of SARS-CoV-2 variants of concern and its implications for vaccine development.
In addition to antibody-mediated neutralization, Fc-dependent effector functions of antibodies directed to SARS-CoV-2 are emerging as an important factor in determining the outcome of infection. This Review highlights the current state of the field and discusses remaining uncertainties regarding Fc-dependent, non-neutralizing functions of antibodies.
In this Perspective, Francis Carbone considers the unique characteristics of the tissue-resident memory T (TRM) cell populations that develop in the lungs. He discusses how the different properties of lung TRM cells may affect immunity to lung infections, including SARS-CoV-2.
This Review discusses recent applications of CRISPR screening to discover intracellular and intercellular regulators of immune cell function in infection, inflammation and cancer, with a focus on the advances of in vivo and single-cell CRISPR screens in immuno-oncology.
In this Perspective, Alain Fischer reflects on the development of gene therapy for patients with inborn errors of immunity. He discusses the challenges the field has faced as well as the progress seen in the past 25 years.
Tumour necrosis factor (TNF) drives inflammatory responses directly by inducing inflammatory gene expression and also indirectly by inducing cell death. This article reviews the various TNF-induced cell death pathways, their mode of execution and the molecular checkpoints that control them, which is revealing new opportunities for the treatment of TNF-mediated diseases.
In this Review, the authors consider the many diverse ways in which the cytokine transforming growth factor-β (TGFβ) can regulate immune responses to tumours. Despite its complex roles, therapies are being developed that target TGFβ for cancer therapy, and the authors discuss the potential of these.
Neutrophils have a central role in the pathogenesis of systemic autoimmune and autoinflammatory diseases, particularly through neutrophil extracellular trap formation. Recent research suggests novel therapeutics targeting these structures that can improve patient outcomes.
Durham and Shamji review the history and future of allergen immunotherapy for established IgE-mediated hypersensitivity to common allergens. They describe the mechanisms of immunotherapy-induced tolerance and the new strategies being explored to achieve safer, more effective, long-term tolerance.
Many viruses, including SARS-CoV-2, can induce cellular senescence and exacerbate the senescence-associated secretory phenotype, leading to detrimental hyperinflammatory responses. Here, Schmitt and colleagues discuss the role of cellular senescence in COVID-19 as well as progress in the development of therapeutic approaches to eliminate senescent cells.
Major human pregnancy disorders arise from the failure of placental trophoblast to access sufficient supplies of maternal oxygen and nutrients. Key to understanding this process are the interactions that occur early in pregnancy between trophoblast cells that invade the decidua and maternal uterine immune cells.
The ancestral strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into a number of variants of concern. In this Review, Wang and colleagues discuss progress in the development and characterization of broadly neutralizing antibodies to SARS-CoV-2, which may lead to new antibody therapeutics and inform the design of next-generation vaccines.
Three-dimensional (3D) genome organization has emerged as an important regulator of gene expression and genomic interaction. Here, the authors explain how 3D genome organization impacts immune cell development and function, and discuss how aberrant genome folding can contribute to immune-mediated disease and cancer.
In this Review, Ng and colleagues examine the clinical, epidemiological and immunological aspects of monkeypox virus (MPXV) infections, with a focus on mechanisms of host immunity to MPXV. The authors also consider the unique epidemiological and pathological characteristics of the current non-endemic outbreak of the virus and discuss vaccines, therapeutics and outstanding research questions.
This Review considers how the biophysical properties of a tissue are able to shape immune cell function through the process of mechanotransduction. There are multiple mechanotransduction pathways that operate in immune cells and the authors highlight these and the emerging field of mechanoimmunology.
There are many reasons why the development of a potent and durable vaccine to HIV-1 is exceptionally challenging, including the large genetic diversity of the virus and its complex mechanisms of immune evasion. In this Review, Haynes et al. discuss strategies for the induction of potent broadly neutralizing antibodies for HIV-1 and the steps that may be necessary for ultimate success.
Here, the authors consider our emerging understanding of COVID-19-associated coagulopathy. They focus on the complex interactions between innate immune, coagulation and fibrinolytic pathways that can lead to potentially life-threatening thrombosis following SARS-CoV-2 infection.
Extracellular vesicles (EVs) are increasingly recognized as having ubiquitous roles in the immune system. This Review focuses on the progress made in the field in the past 5 years, including the roles of EVs in innate and adaptive immunity and their potential use in diagnosis and therapy.
Lorenzo Galluzzi and colleagues discuss the molecular mechanisms through which mitochondrial dysfunction elicits inflammatory reactions, the cellular pathways that are in place to control them and how the dysregulation of these systems contributes to pathology.
In this Review, Gorbunova and colleagues discuss the links between DNA damage, inflammation and ageing. They focus on the implications for premature ageing syndromes and multiple age-related diseases, and highlight potential therapeutic targets.
