Reviews & Analysis

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.

Here, Harvey Cantor and Mari Shinohara propose that the secreted and intracellular isoforms of osteopontin differentially regulate the development of distinct T-helper-cell subsets and, consequently, adaptive immune responses to foreign and self antigens.

Regulatory T (T_Reg) cells are crucial for immune homeostasis, and manipulation of their suppressive functions is a possible avenue for immunotherapy. Here, the authors discuss recent advances in our understanding of how the expression of forkhead box P3 (FOXP3), a T_Reg-cell-specifying transcription factor, is controlled at the molecular level.

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.

Basophils, often regarded as a lesser relative to the mast cell, are now proving to have important, non-redundant roles in immune responses. This Progress article updates us on the latest studies that identify new roles for basophils in allergic reactions and immune regulation.

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.

In this Opinion article, the effector function of annexin A1 in the anti-inflammatory action of glucocorticoids is discussed, and a model to address the opposing effects of glucocorticoids on the expression of annexin A1 by different immune cells is proposed.