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This Review from Wolfgang Kastenmüller and colleagues highlights the heterogeneity that exists among lymph nodes at different anatomical locations. The authors consider the factors that contribute to lymph node heterogeneity and explain the relevance of this for the immune response, particularly in the contexts of vaccination and cancer.
This Review from Wellford and Moseman considers the unique immunology of the olfactory mucosa. The authors describe how stromal cells, innate immune cells and adaptive immune cells cooperate to defend the olfactory mucosa, protecting the host from potentially serious respiratory or neurotropic infections. They also discuss the relevance of olfactory mucosal immunology for the fields of vaccination and neurodegeneration.
The induction of antigen-specific immune tolerance is considered the 'holy grail' of disease management for autoimmunity and organ transplantation. Are we getting any closer to this goal? Here, the authors update us on the current progress and challenges to the therapeutic induction of antigen-specific immune tolerance.
In this Review, Butterfield and Najjar discuss the rationale for combination strategies in cancer, including combinations of different immunotherapies and combinations of immunotherapies with other types of therapies. Moreover, they examine the evolution of biomarker approaches to guide such therapies.
In this Review, Liston et al. discuss the biology of regulatory T cells (Treg cells) in the brain. They consider how Treg cells are recruited to the brain and their anti-inflammatory and reparative functions in brain tissue. Finally, they highlight the potential for targeting brain Treg cells to treat a range of neurological diseases.
This Review outlines the mechanisms by which the microbiota alters the efficacy and immunotoxicity of established and emerging cancer treatments, and discusses the benefits and limitations of microbiota-targeting interventions that are being investigated to improve patient outcomes.
Epidemiological studies and mouse models suggest that stress can affect the evolution, dissemination and outcome of malignancies. In this Review, Ma and Kroemer present insights into the complex neuro-immune interactions that link stress to cancer, with a focus on stress-associated immunomodulatory molecules, and discuss their implications for cancer therapy.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Recent studies have revealed a family of antigen-presenting cells (APCs) marked by the transcription factor RORγt that fundamentally shape immunity, inflammation and tolerance. This article reviews heterogeneity among RORγt+ APCs, their associated functions and the future promise of this new field.
This Review summarizes how the processes of thymic selection together ensure that the T cell repertoire is fully functional and safe. In the thymus, T cell receptor signal strength is integrated with distinct stromal cues to result in positive or negative selection of thymocytes or the generation of regulatory cells.
Microglia are increasingly implicated in the maintenance and regeneration of myelin, which is damaged with normal ageing and in several neurodegenerative diseases. This article reviews the mechanisms by which microglia support and restore myelin health and the factors that influence these crucial microglial functions.
SARS-CoV-2 infection can lead to a diverse array of chronic symptoms, collectively termed ‘long COVID’. In this Review, Altmann and colleagues explore current thinking about the pathophysiology of long COVID and discuss potential immunological mechanisms.
