Review Articles in 2009

Disturbances in the balance between 'good' and 'bad' bacteria that reside in the gut could underlie the development of inflammatory bowel diseases, according to the authors of this Review. They describe how a 'normal' microbiota is required for proper functioning of the immune system.

This article looks at the dysregulation of specific B-cell subpopulations that is associated with chronic HIV infection, with a view to understanding the mechanisms of B-cell pathogenesis in HIV-associated disease and other diseases that are characterized by immune dysfunction.

Tumour necrosis factor (TNF)–TNF receptor pairs that regulate the function of effector T cells have gained prominence as therapeutic targets. Here, Michael Croft describes the biology of four such TNF–TNFR pairs and discusses the implications of targeting them during conditions of inflammation, autoimmunity and cancer.

The homeostatic roles of macrophages in tissue development and maintenance are discussed, and insights are provided into how dysregulation of these primitive functions can be subverted in chronic diseases such as cancer and obesity to contribute to pathology.

Viruses have long been suspected to act as triggers of autoimmune disease. This Review describes the various mechanisms that link viruses to autoimmune responses and highlights how viral infection and immune control can be dysregulated during autoimmune disease.

Infant and elderly humans and mice have a similar vulnerability to common pathogens as a result of the decreased quantity and persistence of antibody responses. This Review looks at the B-cell intrinsic factors and microenvironmental determinants in lymphoid tissue and bone marrow that limit protective B-cell responses in these age groups.

Memory T cells in non-lymphoid tissues provide an important early line of defence against secondary pathogen infection. In this article, the mechanisms involved in the migration, maintenance and function of memory T cells at these peripheral sites are discussed.

Haematopoiesis is driven by complex networks of transcriptional regulators. Among them are the E and inhibitor of DNA binding (ID) proteins, which have important roles in early B- and T-cell development, as well as emerging roles in haematopoietic stem cells and other lymphoid and myeloid lineages.

Signalling through the pre-B-cell receptor is an important checkpoint in B-cell development. But, what are the molecular mechanisms that regulate cell proliferation, immunoglobulin light chain gene recombination and cell differentiation downstream of this receptor?

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells that expands during cancer, inflammation and infection. Here, the authors discuss the mechanisms of MDSC expansion and suppression of T-cell functionin vivo, and describe how these cells might be targeted for therapeutic purposes.

The transcription factor GATA-binding protein 3 (GATA3) is best known as a master regulator of T-helper-2-cell differentiation. However, as part of a network of other transcription factors, GATA3 is also important in determining cell fate at earlier stages of haematopoiesis and lymphoid-cell development.

Recent research indicates that the Notch signalling pathway is important for directing T helper (T_H)-cell differentiation. In this Review, the authors discuss contrasting results showing that Notch can have a role in both T_H1- and T_H2-cell differentiation, and highlight how this information might help to better understand the pathology of T-cell-mediated diseases.

Numerous lineage-specific transcription factors have been linked with T-helper-cell subset specification. But, as discussed here, epigenetic modifications at the gene regulatory elements where these factors bind can also contribute to the regulation of T-helper-cell differentiation and function.

In this Review, the authors discuss how RUNX (runt-related transcription factor) proteins and other key transcription factors work together to direct T-cell lineage choice and CD4⁺T-cell differentiation.

Targeting invariant natural killer T (iNKT) cells could be a good way to boost vaccine responses, according to recent studies reviewed here. Structural and functional analyses of iNKT-cell ligands are helping to direct approaches that harness the capacity of iNKT cells to enhance immune responses.

Scaffold proteins are known to have an important role in signal transduction but their mechanisms of activation are still unclear. In this Review, recent studies that have shed light on the function of cytoplasmic scaffold proteins in immune-cell signalling are discussed.

How B cells see antigen has been an area of intense research for many years. Here, recent advances in our understanding of the specific sites, cells and molecules that are involved in the presentation of antigen to B cells are discussed.

This article discusses the recently identified role of SLAM-associated protein (SAP) — which mediates signals from signalling lymphocytic activation molecule (SLAM) receptors — in regulating interactions between lymphocytes in the thymus and germinal centres, and suggests that SAP and SLAM family members have roles in lymphocyte adhesion that affect development and differentiation.