Reviews & Analysis

This Review describes new roles for the tyrosine kinase SYK in innate recognition of pathogens and tissue damage, cell adhesion, bone metabolism and vascular development, and it discusses the emergence of SYK as a promising therapeutic target in autoimmune diseases and B cell lymphomas.

Recent elegant studies in the mouse have increased our understanding of the origin and function of different macrophage and dendritic cell populations. However, these studies have also highlighted an old debate — how exactly should we classify the cells of the mononuclear phagocyte system? Here, five experts give their thoughts on this topic.

Monoclonal antibodies have shown considerable success as cancer therapeutics. This Focus article describes how these molecules promote tumour eradication by targeting the tumour itself or by targeting cells of the immune system. The authors also discuss the clinical potential of new antibody therapies.

This Review article describes how a subset of nuclear receptors can antagonize pro-inflammatory gene expression, through transrepression mechanisms in macrophages and microglia, and regulate the differentiation and activation of inflammatory helper T cells, particularly T helper 17 cells.

FcγRIIB is the only inhibitory Fc receptor for IgG, common genetic variants of which are associated with susceptibility to autoimmune disease but, also, with protection from severe malaria. Furthermore, understanding the function of FcγRIIB has important implications for the use of therapeutic antibodies.

More than 30 monoclonal antibody-based therapies have been approved for clinical use in the past 25 years. By looking at the strategies that have been used by pharmaceutical companies to develop these products, this Timeline article provides insight into the challenges that will be faced in developing the next generation of therapeutic antibodies.

Therapeutic antibodies have already improved the lives of many people living with autoimmune diseases such as rheumatoid arthritis and Crohn's disease. But there is still room for improvement. Here, the authors review how the current therapeutic antibodies work and how they might be enhanced to increase efficacy and extend their use.

Advances in microscopy and labelling technologies have provided new opportunities for visualizing host–pathogen interactions in action. This Review highlights some of the insights gained from imaging immune responses to pathogens in the context of intact tissues.

A lot of recent research has focused on T helper 17 (T_H17) cells, but their function in the tumour microenvironment has remained controversial. This Review examines the roles of T_H17 cells in tumour immunity and discusses the potential of targeting this subset for cancer therapy.

T helper 2 (T_H2) cells have a central role in protection against helminth infections but are also responsible for the development of asthma and other allergic inflammatory diseases. This Review provides a comprehensive overview of the cellular and molecular mechanisms involved in the initiation and amplification of T_H2-type immune responses in vivo.

This Review discusses recent studies that have identified inositol-1,3,4,5-tetrakisphosphate as a soluble messenger molecule that is essential for the development and function of T cells, B cells and neutrophils through regulating phosphoinositide 3-kinase function and Ca²⁺mobilization.

This article outlines how helminth-derived immunomodulators can subvert pro-inflammatory responses by using host innate immune receptors to trigger divergent signalling pathways in antigen-presenting cells and proposes that these immunomodulators can be used as tools to dissect the pathways required to promote anti-inflammatory responses.

B cells are best known for their ability to produce antibody, but they also contribute to immunity by other mechanisms. Here, the authors argue for the existence of distinct populations of effector and regulatory B cells and discuss how these can modify CD4⁺T cell responses.

Invariant natural killer T (iNKT) cells are thought to be autoreactive by 'design'. Here, Laurent Gapin describes how iNKT cell autoreactivity might be triggered and proposes that several self lipids are probably involved in the positive selection of iNKT cells and the autoreactivity of these cells in peripheral tissues.

As a key regulator of the actin cytoskeleton, Wiskott–Aldrich syndrome protein (WASP) is involved in diverse immune responses, including leukocyte migration and activation. This Review describes how various mutations in mice and humans have led us to a greater appreciation of the many immunological functions of WASP.

Haematopoietic stem cells (HSCs) can reside as dormant cells in endosteal niches in the bone marrow, where they are resistant to certain types of chemotherapy. In this article, the authors suggest that by first awakening dormant HSCs to become actively self-renewing cells, this resistance to chemotherapy could be overcome.

Although the vast numbers of commensal organisms that reside in the human gut are essential for health, they pose a continuous threat of invasion. The intestinal immune system has evolved unique immunological adaptations that help to maintain intestinal homeostasis.

This Opinion article discusses the evidence for and the limitations of the three main models of inflammasome activation. The authors propose that the production of reactive oxygen species might be a common factor downstream of many types of inflammasome activator.

The anti-inflammatory cytokine interleukin-10 (IL-10) has a central role in limiting inflammatory responses to protect against excessive tissue damage. Recent evidence suggests that many types of immune cell can produce IL-10, but how is its transcription regulated in these different cell types?

How are memory cells maintained? In this Review, the authors discuss the emerging role of mesenchymal stromal cells — which organize defined numbers of dedicated survival niches for different types of memory lymphocytes — in the maintenance of immunological memory.