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  • Globig et al. report in Nature that the sympathetic nervous system can signal to T cells to promote T cell exhaustion.

    • Kirsty Minton
    Research Highlight
  • Personalized neoantigen vaccines offer the potential to boost immune response a patient against their specific cancer antigens. Here, Katsikis, Ishii and Schliehe discuss the challenges that currently limit this therapeutic approach, including those related to neoantigen selection and adjuvants, and post-vaccine challenges such as the immunosuppressive tumour microenvironment. Moreover, they consider solutions that could help to overcome these obstacles.

    • Peter D. Katsikis
    • Ken J. Ishii
    • Christopher Schliehe
    Review Article
  • The MHC class I-related protein 1 (MR1) presents specific small molecule antigens to MR1-restricted T (MR1T) lymphocytes. These cells play an important role in infection and cancer, and strategies to target these cells are of considerable therapeutic interest. In this Review, McWilliam and Villadangos provide a comprehensive description of the antigen presentation pathway of MR1, which is fundamental for the understanding of MR1-mediated immunity and the potential therapeutic manipulation of MR1T cells.

    • Hamish E. G. McWilliam
    • Jose A. Villadangos
    Review Article
  • The protective effect of vaccines is often poorest in low-income countries. Here, the authors explore the immunological factors that may explain the geographical variation in vaccine responsiveness and the ways in which they might be modulated to ensure effective vaccination in regions where it is needed most.

    • Marloes M. A. R. van Dorst
    • Jeremia J. Pyuza
    • Maria Yazdanbakhsh
    Review Article
  • The families of tetraspanins and galectins are essential for the organization of molecules on the surface of lymphocytes, and deficiencies in specific family members can lead to impaired immunity, tumour development and autoimmunity. This Review investigates the molecular mechanisms of membrane organization by tetraspanins and galectins, specifically their role in B cell and T cell proliferation, survival and migration, as well as in antibody production and T cell polarization, and discusses potential therapeutic opportunities.

    • Laia Querol Cano
    • Vera-Marie E. Dunlock
    • Annemiek B. van Spriel
    Review Article
  • This Review discusses how the study of novel mouse models of human ADAR1 deficiency has led to the identification of the innate immune receptors recognizing endogenous immunostimulatory double-stranded RNA and their respective downstream signalling pathways that induce autoinflammatory pathology.

    • Richard de Reuver
    • Jonathan Maelfait
    Review Article
  • This Review covers the biology of anti-cytokine autoantibodies and their varied roles in causing, preventing and treating diseases. Recent reports of anti-type I interferon autoantibodies in critical COVID-19 have led to renewed interest in this topic, which offers fascinating insights into the reversibility of immune tolerance and the origins of autoimmunity in otherwise healthy individuals.

    • Aristine Cheng
    • Steven M. Holland
    Review Article
  • A new study shows that even a short-term switch to a low-fibre diet suppresses immunity to bacterial infection and compromises effector T cell responses.

    • Lucy Bird
    Research Highlight
  • Cryptosporidium are protozoan parasites that infect intestinal epithelial cells and can cause severe diarrhoeal disease, particularly in malnourished children. This Review summarizes the immune mechanisms that protect against this parasitic infection, highlighting the innate mechanisms that detect Cryptosporidium at the intestinal epithelium and the adaptive immune mechanisms that mediate resistance.

    • Ryan D. Pardy
    • Bethan A. Wallbank
    • Christopher A. Hunter
    Review Article
  • This Review provides a guide to complement and its emerging roles in processes beyond innate immune defence such as in early development, tissue immunometabolism, tissue regeneration and cancer immunity. Moreover, our improved understanding of its role in disease pathology has opened new options for complement-based therapeutics.

    • Dimitrios C. Mastellos
    • George Hajishengallis
    • John D. Lambris
    Review Article
  • In this Tools of the Trade article, Yury Goltsev and Garry Nolan describe a multiplexed tissue imaging technique called CODEX that enables rapid tissue staining with multiple DNA-barcoded antibodies.

    • Yury Goltsev
    • Garry Nolan
    Tools of the Trade
  • Phagocytosis-mediated cell death — also known as ‘phagoptosis’ — regulates developmental processes, cell turnover and immunity to infections and cancer. Here, Brown summarizes the key molecular interactions involved in cell death by phagocytosis and the relevance of this process for host health.

    • Guy C. Brown
    Review Article
  • Two studies in Nature describe the mechanisms that underlie allergen avoidance behaviour in mice, linking allergen sensing in the gut to a protective behavioural response to repeated ingestion of allergen.

    • Lucy Bird
    Research Highlight