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Immune responses to pathogens and self-antigens show sex-based differences, with female individuals generally more susceptible to autoimmunity and male individuals more vulnerable to infections. In this Review, the authors explore the role of hormones and genetics in shaping immune responses, and discuss genetic and epigenetic contributions to altered X-linked gene expression that affect immune responses.
In this Review, the authors discuss the origins of regulatory T (Treg) cells in the periphery and the mechanisms by which Treg cells are induced, as well as the regulation of the suppressive function of these cells. Moreover, they examine evidence for and mechanisms of Treg cell dysfunction in common autoimmune diseases such as multiple sclerosis, inflammatory bowel disease, systemic lupus erythematosus and rheumatoid arthritis.
This Review highlights new insights into the biology of inflammasomes from the perspective of structural and mechanistic studies, revealing how the supramolecular complexes that activate inflammatory caspases are assembled and regulated, to induce cytokine maturation and release, as well as pyroptotic cell death.
In this Progress article, Fooksman and colleagues review recent advances in the study of long-lived plasma cells, using genetic labelling tools, RNA sequencing and in vivo imaging to characterize the differentiation and survival of this rare cell type in mice and humans.
The first immune-targeted drug for type 1 diabetes (T1D), teplizumab, received regulatory approval by the US FDA in 2022. In this Review, Herold, Walker and colleagues examine the immune mechanisms that underpin T1D and provide an overview of immune-targeted strategies for T1D that are currently in development.
Immune cell engagers — antibody-based molecules engineered to direct immune effector cells to recognize and kill cancer cells — represent a rapidly expanding approach in cancer therapy. Here, the authors bring us up to date with the targets, challenges and opportunities for harnessing the anticancer activities of T cells, natural killer cells and myeloid cells with immune cell engagers.
This Review provides an updated assessment of the expanding family of T cell-activating bacterial superantigens, emphasizing potential roles of these toxins in various disease states as well as their contribution to the evolution of the bacterial pathogens Staphylococcus aureus and Streptococcus pyogenes.
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.
In this Perspective, the authors consider the distinct contributions made by T helper 2 cells and group 2 innate lymphoid cells during the course of a helminth infection. Although anti-helminth drugs are effective, reinfection is common and there are currently no available vaccines — a better understanding of T helper 2 cell and group 2 innate lymphoid cell interplay could lead to new anti-helminth strategies.
Epidemiological evidence indicates that physical exercise can lower cancer incidence and mortality. This Perspective discusses the importance of muscular activity for maintaining a healthy immune system and the potential mechanisms by which exercise affects anticancer immunity.
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.
