Reviews & Analysis

This Review discusses how immune and inflammatory pathways are integrated with those that sense and manage nutrients, dysfunction of which underlies many chronic metabolic diseases, such as type 2 diabetes and atherosclerosis.

Our understanding of the origin, phenotype and function of epidermal Langerhans cells and langerin-expressing dendritic cells has expanded in recent years, details of which, as well as the challenges that remain, are discussed in this Review.

This Review highlights how understanding the mechanisms by which viruses evade and subvert host signalling by pattern-recognition receptors has provided insights into the function of these signalling pathways, the host proteins that are involved and ways in which the pathways might be manipulated therapeutically.

This Review focuses on the structural domains of the autoimmune regulator (AIRE) protein, its nuclear localization, and its role in histone binding and transcriptional elongation, which help to explain the crucial involvement of AIRE in the negative selection of T cells in the thymus.

By proposing new criteria by which macrophage populations can be classified based on functions that are involved in maintaining homeostasis, this Review provides a framework to further elucidate the functions of these cells and their role in disease.

This article proposes that endogenous peptides can enhance the recognition of antigenic peptides by T cells and, based on results from MHC class I- and class II-restricted T-cell systems, that CD4 and CD8 have different roles in the recognition of endogenous peptide–MHC complexes.

These authors express their opinion that we should devote more research attention to uncovering the mechanisms by which a host can tolerate, as well as resist, infection with a pathogen. New drugs to increase tolerance to infection should provide therapies to which pathogens will not develop resistance.

Herpesviruses have evolved numerous strategies to outsmart the host and establish persistent infection. Important targets of viral entry and immunomodulation are the tumour-necrosis factor superfamily proteins. This Review describes the central role of these proteins in both virus survival and host defence.

The tripartite motif-containing (TRIM) proteins are best known for their roles in the restriction of infection by lentiviruses. Here, the authors describe the recent studies that reveal broader antiviral and antimicrobial activities of TRIM proteins, including an involvement in the pathogen-recognition and signalling pathways.

This Review discusses how the diversity of glycan structures that are produced in the secretory pathway and are displayed at the cell surface and in extracellular compartments can have both homeostatic and pathogenic effects on the development and function of the mammalian immune system.

Activation of nuclear factor-κB (NF-κB) is crucial for initiating inflammatory responses. In this Review, Sankar Ghosh and Matthew Hayden discuss the roles of several newly identified regulators of the NF-κB pathway, as well as some old factors that have been assigned new functions.

Antimicrobial proteins are an ancient mechanism of defence against pathogens at skin and mucosal surfaces. As discussed in this Progress article, new studies identify dynamic cross-regulation between cytokines and antimicrobial peptides, which contributes to immunity and homeostasis at these sites.

Sepsis is an overwhelming systemic inflammatory response to severe microbial infection or extensive tissue damage. In this Review, the authors highlight recent molecular data that help to unravel the mechanisms that underlie dysregulation of immune responses in this syndrome.

The anatomy of secondary lymphoid organs defines the ability of an organism to respond to pathogens. In this Review, the authors describe how the functional microarchitecture of these structures is both a determinant and a result of antimicrobial immunity.

What determines whether a developing thymocyte becomes a CD4⁺ or CD8⁺T cell has been an issue of longstanding debate. Here, the authors review the models that have been proposed to explain CD4/CD8-lineage choice and update us on the environmental and transcription factors that might mediate this decision.

The activation of immunoreceptor tyrosine-based activation motif (ITAM)-coupled receptors influences signalling pathways downstream of other receptor types. In this Opinion, Lionel Ivashkiv describes how ITAM-dependent signalling can differentially influence cellular responses to Toll-like-receptor ligands and cytokines.

Atherosclerosis is now widely considered to be a chronic inflammatory disease that is driven by the activities of many leukocyte subpopulations. Here, the authors describe the contribution of different immune-cell subsets to each stage of the disease, revealing complex and dynamic interactions.

Recent research has shown that the interaction of sphingosine-1-phosphate with its receptors (S1PR1–S1PR5) has an essential role in regulating immune responses, not only through the control of immune-cell trafficking but also through effects on immune-cell function. Understanding these effects holds promise for the use of S1PR ligands as immunomodulatory therapeutics.

Vitamins have long been known to have an effect on the immune system. In this Review, the authors describe the effects of vitamins, particularly of vitamins A and D, on immune cells, and discuss how vitamins or their analogues might be applied for the therapy of immune-mediated diseases.

The unfolded-protein response (UPR) protects cells from stress induced by the accumulation of unfolded proteins in the endoplasmic reticulum. As discussed here, an important role for the UPR has recently been described in the immune system, dysregulation of which could potentially contribute to autoimmunity.