Reviews & Analysis

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.

The molecular cloning of the forkhead box P3 (FOXP3) gene led to a renaissance in the field of suppressor T cells (now known as regulatory T cells). In this Timeline article, the authors describe the key events that demonstrated the importance of FOXP3in immune regulation, starting with the discovery of the scurfy mouse some 65 years ago.

Systems biology approaches have revolutionized many fields, including immunology, but analysing and interpreting such large-scale datasets is challenging. Here, the authors describe a novel approach that has been developed to address this issue. It relies on the grouping of co-dependent genes into 'modules', which are then used to build 'fingerprints' that can simplify the analysis of large-scale datasets.

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.

Three models have been proposed to explain the link between T cell division and differentiation — epigenetic changes, asymmetric division and the direct regulation of gene expression by cell cycle factors. In support of the third model, this Opinion article describes cell cycle-independent roles for the cyclin-dependent kinases as regulators of immunologically relevant transcription factors.

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.

Ubiquitylation is an important regulatory process that controls numerous signalling pathways, including those that drive immune responses. As described in this Review, Pellino proteins are E3 ubiquitin ligases that regulate both innate and adaptive immune signalling pathways.

Here, the authors review the expression patterns and function of Fc receptors for IgG (FcγRs) on conventional dendritic cells (DCs), monocyte-derived DCs, plasmacytoid DCs and macrophages in the steady state and at sites of inflammation. They also discuss emerging concepts and areas that require further investigation.

In this Review, the authors describe the unique molecular and functional features of alveolar macrophages that distinguish these cells from other macrophage populations. They discuss how alveolar macrophages are able to shape both pro-inflammatory and tolerogenic immune responses in the lung in order to maintain health at this site.