Regulation of Th2 cytokine gene transcription.

Because of the different functions of IL-4, IL-13 and IL-5, it would perhaps be surprising if common transcriptional mechanisms occur. However, because of the physical proximity of their genes within the human 5q locus, chromatin remodelling during T-cell differentiation may make transcription of all the genes permissible. If co-ordinate regulation were to take place, it might be argued that similar factors might be involved in expression of all of the cytokines. Emerging data on c-Maf and GATA3 regulation of IL-4 and IL-5 respectively argues that diverse proteins may be required for transcriptional activation. Alternatively, these factors may be responsible for regulating transcriptional competence, allowing fine control over generation of particular cytokines depending upon recognition of physiological cues. If competent for transcription, common factors, such as members of the NFAT and/or AP-1 families, may operate to regulate cytokine levels. To support this, we have recently identified a conserved palindrome located within the promoters of the different Th2-type cytokines, which acts as an enhancer of transcription. Central to the capacity to express Th2 cytokines is likely to be the ability to remodel chromatin at the locus. It remains to be determined whether a single factor, or combination of factors acts to regulate this event. It is also unclear what the boundaries of remodelling within the locus are, i.e. whether IL-4 and IL-13 may be within open chromatin and IL-5 in a closed environment, and whether there is a hierarchy which determines whether particular cytokines are preferentially expressed irrespective of competence.