Volume 9 Issue 2, February 2009

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.

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.

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.

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.

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.

Given the different biological functions of the known CD4+ T-cell subsets, an important current area of research is to determine the factors that control T helper (TH)-cell differentiation pathways in different conditions, with a view to understanding how these pathways might be manipulated for therapeutic benefit. This Focus describes the molecular pathways that govern the differentiation of TH1, TH2, TH17 and regulatory T cells.