Review Articles in 2010

Increasingly advanced microscopy techniques are now being widely used to gain a better understanding of lymphocyte activation. This Review provides a guide to the latest imaging technologies, highlighting the advantages and limitations that should be considered when choosing which approach to use.

Recent evidence indicates that the intestinal microbiota has important functions in maintaining intestinal homeostasis through crosstalk with the innate immune system. However, changes in the intestinal microbiota or breakdown of this crosstalk can result in colitis and colitis-associated colorectal cancer.

In this Review, Nicole Baumgarth describes the development and functions of B-1 cells. These innate-like B cells serve as the major source of natural antibody in mice, and can have important roles in defence against mucosal pathogens and in maintaining tissue homeostasis.

Three main types of mechanism have been proposed to explain T cell receptor (TCR) triggering: aggregation, conformation change and segregation. The most recent data on these mechanisms are discussed here, and the authors propose an integrated model for TCR triggering.

Current evidence suggests that immune suppression by CD4⁺CD25⁺FOXP3⁺regulatory T cells is impaired in human autoimmune diseases. The potential mechanisms of such a defect are discussed here, along with the challenges that must be overcome to guide the development of future therapies for these diseases.

Our understanding of the triggers and mediators of sterile inflammation has advanced greatly in recent years. Here, Chen and Nuñez provide us with an up-to-date overview of these advances and discuss their therapeutic implications.

This Review explores how distinct antigen-presenting cell types that reside in lymph nodes can contribute to T cell activation. The authors discuss the recent evidence showing that lymph node stromal cell populations are involved in the maintenance of peripheral immune tolerance.

Asthma is a complex disease that is typically associated with T helper 2 (T_H2)-type inflammation, but it is becoming increasingly clear that other T cell populations can contribute to the disease. Here, the authors describe the functions of distinct T cell subsets in the allergic lung and discuss the implications for future therapies for asthma.

The mechanisms by which local antigen-presenting cells, such as myeloid and plasmacytoid dendritic cells, liver sinusoidal endothelial cells, Kupffer cells and hepatocytes, mediate tolerance to antigens metabolized in the liver are described here. These insights into hepatic tolerance may be harnessed in the clinic for the treatment of various diseases.

When designing the best delivery system for a vaccine, a lot can be learnt from viruses. Here the authors propose that vaccines that mimic key properties of viruses induce optimal immune responses with minimal harmful side effects.

Natural IgM has many roles in the immune system, from protection against infection to regulating autoimmunity. The authors discuss the pleiotropic properties of natural IgM, and the implications for B cell-targeted therapy.

Binding of antigen to the B cell receptor (BCR) on the cell surface results in B cell activation. But how is the information that antigen binding by a BCR has occurred translated across the cell membrane to trigger signalling cascades? And what are the implications for B cell tumorigenesis and autoimmunity?

The extracellular matrix (ECM) has crucial, though often overlooked, roles during the development of an inflammatory response. Lydia Sorokin describes the interactions that occur between leukocytes and the ECM and discusses how aberrant regulation of ECM components may promote chronic inflammation.

Recent research has uncovered new roles for the NOD-like receptors (NLRs) and three types of inflammasome in the inflammatory response to viral infection, the importance of which is highlighted by the viral inhibitors that target these pathways.

Immune responses in the genital tract are different to those at other mucosal surfaces. In this Review, Akiko Iwasaki explains how the anatomy of the genital mucosa affects the immune response to viral infection and describes the challenges that are faced in the development of vaccines against sexually transmitted viruses.

This article discusses the current models of how ligation of inhibitory receptors on NK cells by host MHC class I molecules can result in 'educated' NK cells and the recent insights into the signalling pathways that are involved. How MHC class I molecules can regulate receptor repertoire formation in NK cells is also discussed.

What factors determine the development of γδ versus αβ T lineage cells from common thymocyte progenitor cells? Here, the authors discuss the two prevailing models for γδ versus αβ T cell development and discuss recent evidence that supports a T cell receptor signal strength model for γδ T cell lineage specification.

NFAT transcription factors are expressed by most immune cells and have critical roles in regulating immune responses. This Review describes recent insights into the NFAT-mediated regulation of distinct immune cells and details our increasing understanding of the importance of the NFAT family during tumorigenesis.

This Review focuses on the earliest steps in the formation of lymphoid tissues during embryogenesis, describing the cellular and molecular requirements. The authors compare this with the development of lymphoid structures in mucosal tissues after birth and of tertiary lymphoid organs at sites of chronic inflammation.

Virus infection in a wide range of eukaryotic host species results in the production of virus-derived small RNAs (such as small interfering RNAs) that specifically target the virus genome through RNA interference and related RNA silencing mechanisms. In this manner, virus-derived small RNAs mediate a form of antiviral immunity.