The epithelia of the skin and mucosae have a crucial role in providing a protective barrier against the constant threat of environmental insults, and accordingly, breach of this barrier by microorganisms or allergens can have adverse effects.

Two articles in this issue focus on how understanding events at epithelial-cell surfaces will be crucial in determining the mechanisms involved in epithelial diseases, such as asthma, eczema and intestinal inflammation. By bringing together evidence from recent genetic studies, William Cookson (on page 978) points out that many genes that confer increased susceptibility to allergic diseases are expressed in the epithelium. He suggests that if we are to design effective treatments for these diseases, our efforts should be concentrated on understanding how allergens invoke immune responses at the level of the epithelium. Similarly, understanding the crosstalk between microorganisms and intestinal epithelial cells is the focus of Philippe Sansonetti's article on page 953. He describes the mechanisms that allow us to 'tolerate' the constant presence of commensal microorganisms while efficiently mobilizing active immune defences against pathogenic microorganisms.

Elsewhere in this issue, the focus turns to immune regulation at the nuclear level. In eukaryotic cells, access of transcription factors to DNA is hindered because the DNA is tightly packaged into chromatin. Tian Chi (on page 965) explains how chromatin-remodelling complexes, such as BAF complexes, have a crucial role in mediating access to DNA and regulating the transcription of genes of the immune system. After a gene undergoes transcription, the mRNA can be subjected to alternative splicing. On page 931, Kristen Lynch discusses the numerous examples of alternative mRNA splicing in the immune system and its role in regulating T-cell activation and effector function.