Reviews & Analysis

The discovery that patients with asthma can be dichotomized according to levels of type 2 inflammation, and hence their response to inhibitors of this pathway, promises to enhance our understanding of pathogenic mechanisms and personalized therapies.

Here, two receptors that inhibit T cell functions — programmed cell death protein 1 (PD1) and lymphocyte activation gene 3 protein (LAG3) — are reviewed. Their mechanisms of action are discussed in the context of clinical blockade for cancer therapy and potential biomarkers of the efficacy of therapeutic blockade are proposed.

This Review describes how key metabolic processes are differentially regulated in dendritic cells (DCs), both during their development and during their participation in active immune responses. The authors discuss the importance of these changes in cellular metabolism for DC function and also explain how both intracellular and extracellular metabolites shape DC biology.

In this Review, the authors describe the key epigenetic events that are associated with the differentiation and function of cells of the myeloid lineage, with a particular emphasis on monocytes and macrophages. They detail the epigenetic enzymes that control these events and discuss emerging data that show the importance of epigenetic regulation for 'memory-like' behaviour in innate immune cells.

Periodontitis has been linked to systemic inflammatory conditions such as rheumatoid arthritis. In this Review, the author summarizes these links and discusses the mechanisms of microbial immune subversion that tip the balance from homeostasis to disease at oral or distant sites.

Being able to useDrosophila melanogaster to study immunity on a whole-organism level is proving to be highly valuable in deciphering the links between systemic metabolic and hormonal changes and the immune response. Here, the authors describe the insights gained so far into organism-wide immune regulation and the future directions for research in D. melanogaster.

The recent realization that the airways harbour a steady-state microbiota necessitates a shift in our understanding of respiratory health and disease, drawing from similarities with host–microorganism relationships in the intestines.

This Review describes the biology of the interleukin-20 (IL-20) subfamily of cytokines. The authors detail the cellular sources and targets of these cytokines, and explain their key roles in promoting immunity to infections and driving tissue repair. They also discuss the emerging roles for IL-20 subfamily cytokines in metabolism and tumour immunology.

Recent studies have shown that complement activation is not confined to the serum but also occurs within cellular compartments. This has led to an emerging understanding that complement components can intersect diverse cellular metabolic and effector pathways. Here, the authors propose that the different locations of complement activation dictate its diverse functions.

This Opinion article proposes that higher-order protein complexes — referred to as supramolecular organizing centres (SMOCs) — form on specific organelles by nucleated polymerization downstream of innate immune receptors to amplify the signal and reach a response threshold.

In this Opinion article, the authors discuss how the induction of regulated cell death and inflammatory pathways may lead to an auto-amplification loop that causes tissue damage and organ failure. They propose that targeting both processes could be useful for treating a broad range of clinical conditions with an inflammatory basis.

The closely related oxysterols, 25-hydroxycholesterol and 7α,25-dihydroxycholesterol, have important functions in innate and adaptive immune responses, ranging from antiviral and inflammation-regulatory effects to a role as a guidance cue for B cells and dendritic cells.

Malaria infections can result in deleterious activation of innate immune cells. In this Review, the authors summarize how thePlasmodiumparasite is recognized by innate immune receptors, and discuss the role of these receptors in host resistance to infection and in the pathogenesis of malaria.

Although the MHC class II-mediated modulation of CD4⁺ T cell responses is typically associated with dendritic cells, macrophages and B cells, other cell populations are also suggested to show such behaviour. The authors discuss these atypical antigen-presenting cells and question their relevance to immune responses in vivo.

Chronic viral infections and malignant tumours are associated with the development of T cells that have an 'exhausted' phenotype and that are thought to be severely functionally impaired. In this Opinion article, the authors propose that the exhausted phenotype is actually a functional adaptation to cause minimal tissue damage while still mediating a critical level of pathogen control.

This Review details how the activation of airway epithelial cells and innate immune cells can drive chronic diseases of the lungs, such as asthma and chronic obstructive pulmonary disease. The authors discuss how a better understanding of the mechanisms involved is leading to new treatments for these diseases.

In this Review, the authors describe the unique and varied immune microenvironments that are found along the length of the intestinal tract. They explain how both host-derived and environmental factors shape this regional specialization and discuss the implications for intestinal pathologies, such as inflammatory bowel diseases and cancers.

Siglecs are sialic acid-binding cell-surface proteins that can help the immune system to distinguish between self and non-self. In this Review, the authors describe how Siglecs can modulate immune cell signalling, outline the role of Siglecs in disease and discuss targeting Siglecs for therapeutic purposes.

Reiner and Adams propose a deterministic scenario for diversifying the fates of the cellular progeny of a single antigen-selected lymphocyte, with an element of plasticity based on the nature of the pathogen and the number of responding cells.

Studies in mice indicate that targeting antigens to dendritic cells (DCs) can elicit strong CD4⁺T cell responses. In this Opinion article, the authors summarize the existing DC-targeting approaches; they discuss whether these vaccines are superior to current vaccines and what future studies should entail to successfully introduce these vaccines into a clinical setting.