T(h)2-specific DNase I-hypersensitive sites in the murine IL-13 and IL-4 intergenic region

IL-4 and IL-13 are cytokines preferentially produced by T(h)2 cells, and their genes are located in close proximity on human chromosome 5 and mouse chromosome 11. To identify potential regulatory elements that confer T(h)2-specific expression of IL-4 and IL-13 genes, we constructed a physical map of the IL-13/IL-4 locus and conducted DNase I-hypersensitive (DH) site analysis using T(h) clones and in vitro-differentiated effector T(h) cells obtained from TCR transgenic mice. Three DH sites, HSS1, HSS2 and HSS3, were identified within the intergenic region between IL-13 and IL-4 genes. HSS3 was observed both in T(h)1 and T(h)2 cells as well as CD4⁺ naive T cells, while HSS1 and HSS2 were detected exclusively in T(h)2 cells. The correlation between differentiation into T(h)2 subtype and the appearance of HSS1 and HSS2 suggests that these regions may play a role in subtype-specific expression of the IL-13/IL-4 locus.