BACKGROUND: Asthma is a Th2 cell-driven inflammatory disease and a major public 
health concern. The cis-acting element Rad50 hypersensitive site 6 (RHS6) in the 
Th2 locus control region is essential for regulation of the Th2 cytokine genes; 
however, its role in allergic airway inflammation and underlying molecular 
mechanisms of the regulation by RHS6 are poorly understood.
OBJECTIVE: We sought to understand the role of RHS6 in the development of 
allergic airway inflammation and its molecular mechanism for Th2 cytokine 
expression.
METHODS: We used an ovalbumin-induced allergic inflammation model with 
RHS6-deficient mice to examine the role of RHS6 in this process. To examine 
molecular mechanism of RHS6 for Th2 cytokine expression, we used DNA affinity 
chromatography and mass spectrometry, quantitative RT-PCR, ELISA, intracellular 
cytokine staining, chromatin immunoprecipitation, and co-immunoprecipitation.
RESULTS: Deletion of RHS6 caused a dramatic resistance to allergic airway 
inflammation. RHS6 recruited transcription factors GATA3, SATB1, and IRF4, which 
play important roles in expression of all three Th2 cytokine genes. RHS6 
deficiency caused inhibition of transcription factor-induced Th2 cytokine gene 
expression.
CONCLUSION: RHS6 is a critical regulatory element for allergic airway 
inflammation and for coordinate regulation of Th2 cytokine genes by recruiting 
GATA3, SATB1, and IRF4.