Review Articles in 2014

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.

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.

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.

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.

There is a growing appreciation of how the host inflammatory response is intricately entwined with the various forms of programmed cell death. This Review discusses the signalling mechanisms that link these processes, with a particular focus on how the key mediators of cell death, such as the caspases, are integrated into innate signalling modules.

T helper 17 (T_H17) cells promote protective immune responses against infection, particularly at barrier sites, but they can also have pathogenic roles in inflammatory diseases. In this Review, the authors describe the factors that control the development and maintenance of T_H17 cells, and discuss their diverse functions in both health and disease.

In this Review, the authors describe how Toll-like receptors (TLRs) assemble with signalling adaptor proteins to form higher-order scaffolds that signal in response to pathogen sensing. Productive TLR signalling involves cooperative assembly, post-translational modification and subcellular localization of the components of the signalling complexes.

The butyrophilins are members of the immunoglobulin superfamily that have previously been poorly understood, however they are now emerging as key modulators of the immune system. Here, the authors describe the diverse ways in which butyrophilins can modify immune cell activity and discuss the potential of targeting this family for therapeutic purposes.

T cell development can be divided into three major regulatory phases by the checkpoints that occur at commitment to the T cell lineage and at β-selection. The three phases are each governed by different gene networks that confer distinct cellular characteristics. The correct developmental programme depends on the sequential operation of these gene networks, and cells that fail to enforce the boundaries between phases may be predisposed to leukaemic transformation.

T cell subsets have unique metabolic needs. In this Review, the authors explain how metabolic pathways are interconnected with signalling pathways that mediate the activation and differentiation of discrete T cell subsets. They suggest that a better understanding of this complexity will lead to more targeted therapies for immune regulation.

In this Review, the authors discuss how innate immune mechanisms can contribute to the development of neurodegenerative disease. They suggest that both local and systemic inflammation can drive pathological microglial cell activity, thereby leading to neuronal cell dysfunction and disease.

Follicular dendritic cells (FDCs) in lymph nodes support the development of high-affinity antibody responses by retaining antigens at their cell surface for long periods of time. Although FDCs are generally regarded as 'accessory cells' in the germinal centre, recent data suggest that they have more active roles in the development of humoral immune responses. This Review focuses on our current understanding of FDCs.