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  • 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.

    • Lucy Bird
    Research Highlight
  • 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.

    • Ananda Shanti Mirchandani
    • Manuel Alejandro Sanchez-Garcia
    • Sarah Ruth Walmsley
    Review Article
  • 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.

    • Satish Kumar Tiwari
    • Wei Jie Wong
    • Florent Ginhoux
    Review Article
  • 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.

    • Thomas Boehm
    Perspective
  • 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.

    • Matthew J. Sweet
    • Divya Ramnath
    • Ronan Kapetanovic
    Review Article
  • 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.

    • Ludger Klein
    • Elisabetta Petrozziello
    Review Article
  • 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.

    • Victor Bosteels
    • Sophie Janssens
    Review Article
  • 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.

    • Søren E. Degn
    • Pavel Tolar
    Review Article
  • 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.

    • Anne Spurkland
    World View
  • 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.

    • Rebecca C. Coll
    • Kate Schroder
    Review Article
  • 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.

    • Vuk Cerovic
    • Oliver Pabst
    • Allan McI Mowat
    Review Article
  • In this Tools of the Trade article, Mayar Allam and Ahmet Coskun describe how they combined spatial metabolomics and proteomics profiling — in a framework they call scSpaMet — to explore, at the single-cell level, how metabolic profiles vary by location and in disease.

    • Mayar Allam
    • Ahmet F. Coskun
    Tools of the Trade