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Activation of the unfolded protein response during immune cell activation has emerged as making an essential contribution to the response to infection and inflammation. In this Review, the authors discuss where, how and when a disbalanced unfolded protein response can become pathological and thus a potential therapeutic target.
A disseminated tumour cell will grow only if it arrives at a ‘fertile’ distant site, which as Ana Luísa Correia posits is determined largely by the immune context at the site. Site-specific differences in local immune cell types, ratios and spatial locations influence whether a disseminated tumour cell establishes metastases or is kept dormant.
In this Review, Marco Colonna provides a comprehensive summary of the triggering receptor expressed on myeloid cells (TREM) family of receptors. TREMs are important for modulating signalling in myeloid cells and have now been implicated in many different disease settings, including inflammatory diseases, autoimmunity, neurodegeneration and cancer.
Neonatal Fc receptor (FcRn) supports host defence through its role in antibody recycling and transcytosis, as well as by regulating immune effector cells together with classical Fc receptors for IgG. However, in autoantibody-mediated disease, these activities can be harmful. FcRn-blocking strategies are now showing promise in the clinic.
In addition to their well-established role in haemostasis, platelets also have an active role in the immune response. Here the authors summarize the evidence linking platelet activation to immune dysregulation and organ damage in immune-mediated inflammatory diseases, and discuss the therapeutic potential of targeting platelets.
Galectins can modulate immune cells by binding to glycosylated proteins and lipids on the cell surface, or intracellularly via carbohydrate-dependent or carbohydrate-independent interactions. This Review explores the diverse ways in which galectins affect immunity and discusses the challenges in the field.
The authors propose a new grouping of glomerulonephritis disorders based on their underlying immunopathogenesis, with a view to improving diagnosis, mechanistic understanding and treatment of these immune-mediated kidney diseases.
This Review synthesizes our current mechanistic understanding of the cellular and molecular determinants of tissue-specific antifungal host defences derived from animal models of fungal disease, humans with fungal infection-manifesting inborn errors of immunity and patients treated with fungal infection-promoting, immune-targeted biologics.
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.
