Review Articles in 2011

This Review describes how next-generation sequencing has enriched our knowledge of how STAT proteins regulate cytokine-mediated T helper cell differentiation through direct DNA binding and by affecting epigenetic modifications.

This Review provides a very accessible summary of the mechanisms of V(D)J recombination, including the role of the chromatin architecture and histone modifications in determining accessibility for RAG (recombination activating gene) protein binding. The authors discuss potential models for RAG specificity and summarize the major outstanding questions in this field.

In this article, Luigina Romani describes the immune mechanisms that have evolved to recognize and respond to fungi. She explains how the failure of either pro-inflammatory or tolerogenic immune responses can lead to the development of fungal diseases.

This Review focuses on how HIV infection affects the functions of dendritic cells and natural killer cells. The authors propose that a better understanding of the roles of these innate immune cells during HIV infection could lead to improved antiviral strategies.

Synergistic and antagonistic signalling crosstalk between receptors of the innate immune system maintains a fine balance between protective immunity and inflammatory pathology. This Review article looks at how pathogens can manipulate this signalling crosstalk to dysregulate the host immune response for their benefit.

Recent studies have shown that caspase 1 activation by inflammasomes controls a set of non-canonical effector mechanisms that might contribute to the immune response during infection and autoimmunity. These mechanisms include unconventional protein secretion, pyroptosis, regulation of metabolic pathways and restriction of bacterial replication.

Here, Wolfgang Junger discusses the importance of purinergic receptor signalling for fine-tuning immune cell responses. Autocrine signalling through purinergic receptors can both amplify and inhibit leukocyte functions; the author explains how this is important for sensing chemotactic gradients and detecting rare antigens.

Toll-like receptors (TLRs) are central to the induction of pro-inflammatory responses, but their signalling pathways must be tightly regulated. As discussed in this article, an emerging level of fine-tuning is mediated by microRNAs, several of which are induced by TLR signalling.

Here the authors describe how multiple pattern recognition receptors, at the host cell surface, in endosomes and in the cytoplasm, are involved in detecting herpesviruses. How do they each contribute to immune defence against the virus, and how does the virus evade this detection and persist in the host?

There is currently a lack of consensus as to whether defects in natural killer T (NKT) cells contribute to human diseases. Here, the authors explain how contrasting results may have arisen and suggest more stringent methods to improve NKT cell analysis and therapeutic prospects.

This Review describes the recent progress we have made in understanding how regulatory T cell responses are tailored according to the particular nature of the immune environment. The authors discuss the implications for developing new therapies that harness the functions of regulatory T cells.

Adipose tissues and infiltrating immune cells produce numerous bioactive factors that have pro-inflammatory or anti-inflammatory activities. Here, the authors describe how dysregulated production of these so-called adipokines can contribute to the pathogenesis of obesity-linked metabolic disease.

The cellular stresses that are proposed to underlie impaired insulin secretion and sensitivity in type 2 diabetes can also trigger inflammation. Here, the authors explain how inflammatory mechanisms are involved in the pathogenesis of type 2 diabetes and how this knowledge is directing immunomodulatory strategies for treating the disease.