Reviews & Analysis

Notch signalling has well-described roles in lymphocyte development. More recently, it has become apparent that Notch is also crucial for innate immune cells and for mature lymphocyte responses. Here, the authors discuss our current understanding of how Notch contributes to both innate and adaptive immune responses.

Recent research has shed light on the complex regulation and functions of reactive oxygen species (ROS) signalling. In this Review, Nathan and Cunningham-Bussel provide an update on ROS biology, and they highlight some important roles for ROS in innate and adaptive immunity.

Studies of the establishment of definitive haematopoiesis in various model organisms have identified signalling requirements for the specification of haematopoietic stem cells (HSCs); this information could inform attempts to generate HSCsin vitrofor therapeutic use.

There has been much interest in understanding how the gut microbiota can influence health and disease. Here, Gabriel Núñez and colleagues provide a comprehensive overview of the mutualistic relationship between the host immune system and microbiota, describing ways in which this relationship influences homeostasis and disease.

Here, the authors describe how T cell trafficking to distinct tissues is regulated under inflammatory and non-inflammatory conditions. They explain how the unique migratory properties of different T cell populations are intimately connected to their functions and, furthermore, discuss whether the ever-expanding nomenclature for T cell subsets is a help or a hindrance to immunologists.

The ageing of haematopoietic stem cells (HSCs) might underlie immune system-associated pathologies such as autoimmunity and leukaemias in the elderly. In this Review, the authors summarize the cell-intrinsic and cell-extrinsic mechanisms that have been associated with HSC ageing and discuss how these mechanisms could be targeted to rejuvenate HSCs.

Mast cells and basophils are associated with protective immunity to helminths, but can also drive pathological immune responses in asthma and allergy. This Review covers the recent advances that have improved our understanding of the origins of these cells and of their biological functions in both health and disease.

The lymphotoxin signalling pathway is best known to immunologists for its crucial roles in promoting the development and the organization of lymphoid organs. However, lymphotoxin also contributes to protective immunity against infection and can regulate the intestinal microbiota. The authors discuss these and the other lesser known immune functions of lymphotoxin.

Type 1 diabetes (T1D) was described as an autoimmune disease more than 25 years ago, but the mechanisms involved in this disease are not yet completely understood. Here, the authors review the current models of how T1D disease develops and discuss the steps that will need to be taken to develop more successful therapies for patients.

The first signalling molecules that are activated following T cell receptor engagement feed into an intricately branched and tightly regulated network of signalling cascades that influences T cell activation and differentiation. Perturbation of this diversified network can result in dysregulated T cell signalling and the development of autoreactivity.

If an exogenous antigen such as gluten can drive the autoimmune features of coeliac disease, such as the production of autoantibodies and the destruction of a specific tissue type, should we be looking more closely at the possibility that other autoimmune diseases are driven by exogenous, not self, antigens?

The central role of co-stimulatory and co-inhibitory receptors in T cell biology has been proven by the effective therapeutic targeting of some of these molecules. However, the molecular aspects of T cell co-stimulation and co-inhibition are far from being fully understood. Here, the authors discuss emerging concepts in T cell co-signalling.

Population genetics informs about how genes have evolved under varying selective pressures. The analysis of such selection signatures in innate immune genes, including genes encoding pattern-recognition receptors and their downstream effector molecules, provides helpful insight into the roles of these genes in host immunity and their links to disease.

In this Opinion article, the authors present a model of the barrier systems that control immune cell access to immune-privileged sites. They suggest that immune cell trafficking through 'true' endothelial barriers in the parenchyma results in destructive inflammation, whereas 'educational' epithelial gates allow for selective trafficking to facilitate immunosurveillance of these sites.

It is becoming clear that the immune functions of neutrophils are more complex than once thought. Here, the authors provide an updated version of the classical neutrophil recruitment cascade and discuss the pro-inflammatory and anti-inflammatory roles of these cells in different immune settings.

Lynda Stuart and colleagues discuss the ability of animals to sense perturbations in host cells caused by pathogen effectors. On the basis of recent mechanistic evidence, they suggest that such effector-triggered immunity might be as widespread in animals as in plants.

Intravenous immunoglobulin (IVIG) therapy is used to treat immunodeficient patients, but it can also suppress various autoimmune and chronic inflammatory diseases. Despite the clinical success of IVIG therapy, its mechanisms of action remain controversial. Here, the authors discuss the potential models for how IVIG mediates its immunomodulatory effects.

Here, the authors discuss recent evidence indicating that components of the immune system are under the control of circadian rhythms. The circadian oscillations of immune mediators may allow the host to anticipate threats more efficiently but may also contribute to circadian exacerbations of chronic diseases. In addition, these circadian rhythms should be considered in the design of preclinical animal models, when harvesting human tissue samples and in vaccine administration.

This Review critically assesses six signatory roles of the often overlooked γδ T cells that may collectively distinguish these cells from αβ T cells, and thereby define their unique contributions to lymphocyte biology.

Marginal zone B cells are strategically positioned at the interface between the circulation and the white pulp of the spleen, where they can mediate a rapid, innate-like humoral response against both pathogens and commensals that breach the mucosal barrier. Understanding the interplay of these cells with other immune components and the species-specific differences between mice and humans is of clinical importance.