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This Review provides an overview of arginine and arginase function in immune cells, at the steady state and during disease. It considers the relevance of this pathway for metabolic, immune and genetic regulation, together with possible therapeutic interventions.
The aryl hydrocarbon receptor (AHR) can sense and initiate immune responses to many different infectious organisms. Here, Moura-Alves and colleagues review the role of the AHR in host–pathogen interactions and explore the therapeutic potential of targeting the AHR in the context of different infectious diseases.
Febrile temperatures disrupt metabolism and induce DNA damage disproportionately in T helper 1 cell subsets. Cells that survive apoptosis and adapt by increasing their mitochondrial mass and DNA damage responses gain enhanced effector functions.
CD8+ T cells are functionally impaired during chronic HBV infection. Recent findings from preclinical models and studies of chronically infected humans have revealed surprising insights into the nature of the T cell dysfunction, which may open new avenues for therapeutic intervention.
Oxygen levels vary throughout the body and immune cells must adapt to these changes, both during homeostasis and in disease. Here, the authors discuss the impact of physiological subatmospheric oxygen levels (physioxia) as well as disease-related hypoxia on immune cell responses. They consider the therapeutic relevance of understanding how oxygenation affects immune responses in various diseases, including tuberculosis, COVID-19 and cancer.
Macrophages are associated with many human diseases but are challenging to study in vivo. Here, Ginhoux and colleagues discuss how iMacs — macrophages generated from induced pluripotent stem (iPS) cells — can enable disease modelling, including through the use of patient-derived iPS cells and 3D organoid co-culture systems. Ultimately, these iMac-based approaches can improve our understanding of macrophage biology in both health and disease.
Technological advances in cellular and molecular immunology are providing unprecedented new insights into evolutionary immunology. This Perspective highlights new insights into the immune systems of different vertebrate species and discusses emerging general principles of immune system function.
Macrophages are innate immune sentinels providing frontline defence against infection. This Review describes the inducible mechanisms used by macrophages to kill bacterial pathogens and/or inhibit their growth and outlines how this knowledge might be exploited in the design of host-directed therapies.
For effective central T cell tolerance, developing thymocytes must encounter a diverse range of self-antigens presented by various thymic cells. Here, the authors describe how medullary thymic epithelial cells, dendritic cells and B cells are uniquely adapted through promiscuous gene expression, strategic positioning and inflammatory signals, which shape the peptide–MHC ligandomes and extend self-antigen visibility in the thymic microenvironment.
Dendritic cells (DCs) act as gatekeepers between immunity and tolerance. Initially, it was postulated that mature DCs promote effector T cell responses and immature DCs promote tolerance. Recent studies have shown instead that two distinct modes of DC maturation exist — homeostatic and immunogenic. Here, Bosteels and Janssens discuss our current understanding of homeostatic DC maturation and how this contributes to immune tolerance, with a focus on the cDC1 compartment.
Starkl et al. show that mast cells have a key role in the metabolic network that underlies postoperative pain and demonstrate that this can be therapeutically targeted in mouse models.
Francesca Di Rosa works on T cells and is committed to science outreach. Together with Adrian Hayday, she recently conceptualized and delivered the exhibit ‘Vaccination, a time machine’ at the Royal Society Summer Exhibition in London. Here, she shares her thoughts on how to communicate a core scientific content with artistic and historical input, according to her ‘5C’ formula.
The mechanisms by which antigen triggers B-cell activation are incompletely understood. In this Review, Degn and Tolar discuss the different models of B-cell receptor triggering that have been proposed over the years in the light of recent insights.
Anne Spurkland is a professor of medicine, and her research interests include T cell activation and autoimmunity. She is also an avid baker of cakes that everyone can have and eat too, irrespective of allergies and dietary preferences. This latter passion propelled her into national fame as one of Norway’s most visible experts on immunity and viruses during the COVID-19 pandemic.
Inflammasomes are signalling machines that drive inflammation. This Review highlights the signalling biology of inflammasomes and how we can use small molecules or biologics to block pathological inflammasome signalling to treat or prevent diverse human diseases.
Oral tolerance describes how the oral administration of harmless antigens (such as dietary proteins) leads to systemic immune unresponsiveness to these antigens. Its failure can lead to conditions such as food allergies. This Review from Cerovic, Pabst and Mowat explores new insights into the mechanisms of oral tolerance, discussing how ingested antigens enter and are processed in the intestine, the roles for unique antigen-presenting cells and the induction of immunosuppressive T cell populations. The authors also examine the maintenance of tolerance to bacterial antigens in the intestine, and they discuss the mechanisms behind the failure of oral tolerance and potential clinical interventions.
