Review Articles in 2014

Inflammation can promote the development of lymphoid structures in tissue sites at which they do not normally occur. Here, the authors discuss how these ectopic lymphoid-like structures arise and, furthermore, how they affect immune responses in the setting of infection and disease.

Mast cell granules contain numerous immunomodulatory compounds that are rapidly released in various inflammatory settings. Here, the authors describe the composition, biogenesis and maturation of mast cell granules, and they focus on the biological effects of the mast cell proteases that are released.

In this Review, the authors highlight the importance of the diverse mechanisms that regulate the expression of innate immune genes post transcription. These regulatory mechanisms act at the level of mRNA splicing, mRNA polyadenylation, mRNA stability and protein translation, and they are important for controlling the magnitude and duration of inflammatory responses.

Research into the role of commensal microorganisms in influencing the immune system has mainly focused on bacterial communities. Here, the authors review recent studies that highlight the importance of commensal fungi and how the immune system interacts with these communities at different body sites.

Our understanding of the ontogeny of monocytes and macrophages, as well as their maintenance in the steady state, has recently undergone a renaissance. Here, Ginhoux and Jung discuss the evidence that has changed our view of the relationship between monocytes and tissue macrophages during development and in the steady state.

Recent studies of ontogeny and gene expression have enabled the discrimination of dendritic cell and macrophage subsets in mouse skin and the identification of their human counterparts, which has led to a growing appreciation of the functional specialization of these subsets.

Here, the authors describe the key characteristics of the different antigen-presenting cell (APC) populations that govern T cell development in the thymus. They discuss how the interactions that occur between thymocytes and thymic APCs shape the mature T cell repertoire, and how they subsequently affect the nature of peripheral immune responses.

The recognition of influenza virus by multiple pattern recognition receptors initiates numerous defence mechanisms to control disease through their effects on antiviral resistance and disease tolerance. Here, the authors review these mechanisms and discuss how the treatment of influenza virus-initiated diseases should promote both of these protective strategies to improve host fitness.

This Review covers the cellular sources and immune functions of the various cytokines that have been associated with inflammatory bowel disease (IBD). The author details how the dysregulated production of pro-inflammatory and anti-inflammatory cytokines can drive IBD pathology, and discusses the feasibility of targeting different cytokines for the future therapy of IBD.

A summary of the molecular and cellular events that coordinate the markedly increasedde novoproduction of neutrophils in response to systemic microbial infection.

Immune homeostasis in the skin requires dynamic crosstalk between epithelial, stromal and immune cells, which is influenced by environmental insults and commensal microorganisms. Here, the authors highlight recent studies that provide an insight into the immunoregulatory mechanisms that mediate host defence and prevent chronic inflammation in the skin.

IgE provides protective immunity against helminths, but is also involved in the pathogenesis of allergic diseases. In this Review, Wu and Zarrin discuss recent studies using different IgE reporter mice, as well as other genetically modified mice, that have provided new insights on the cells and pathways involved in the production and regulation of IgE, and highlight the areas in need of additional studies.

This Review follows neutrophils and T cells as they journey from the blood into tissues in search of sites of infection or injury. It highlights the mediators, which form temporally and spatially coordinated gradients within the tissues, and the mechanisms, including physical structures, that guide this directional migration.

Here, the authors describe the immune mechanisms that are involved in pain, one of the key features of inflammation. They explain how the immune and nervous systems interact to initiate and propagate pain, and discuss the immune components that can be targeted for alleviating pathological pain in patients.

Intestinal epithelial cells (IECs) promote gut homeostasis by coordinating the segregation and regulation of commensal microorganisms and the host immune system. This Review highlights the diverse and multifaceted roles of IECs in barrier function, and in their regulation of innate and adaptive immune cell function and homeostasis in response to microbial colonization.

Extracellular vesicles, including exosomes, provide a means of intercellular communication for immune regulation. Here, the authors describe how the proteins, nucleic acids and other molecules that they carry influence immune responses, and explore their potential use in the treatment of inflammatory and autoimmune diseases, and cancer.

The immune regulation of liver fibrosis (particularly the distinct and opposing roles of macrophage subsets) provides an informative model of the endogenous mechanisms that mediate the resolution of fibrosis and the restoration of tissue homeostasis.

Regulatory T (T_Reg) cells are crucial for maintaining immune homeostasis in the body, with recent data showing that distinct T_Reg cell subsets become specialized to function in different tissues. Here, Liston and Gray highlight the need to regulate the number and function of the T_Reg cells themselves, and they describe the dynamic processes that achieve this homeostasis and functional specialization of T_Regcell subsets.

The removal of apoptotic cells by phagocytes is essential for the maintenance of tissue homeostasis and is usually immunologically silent. However, dysregulation of this process is associated with numerous inflammatory and autoimmune diseases, and thus the therapeutic manipulation of apoptotic cell clearance by phagocytes may be a means to treat these diseases.

Much research intoToxoplasma gondii infection has concentrated on adaptive T helper 1 cell responses. More recently, scientists have focused on the innate immune pathways that enable control of T. gondii infection. This Review compares the innate immune response to T. gondiiin mice and humans, with a particular focus on Toll-like receptor-dependent pathways.