Comprehensive Analysis of Stat5a Target Genes in Th2 Cell Differentiation

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Recent studies have shown the importance of Stat6-independent pathway in Th2 cell differentiation. We have previously shown that the simultaneous disruption of Stat6 and Stat5a resulted in the complete inhibition of Th2 cell differentiation and allergic airway inflammation. Therefore, Stat5a seems to be essential for Stat6-independent Th2 cell differentiation and might be a target for the treatment of allergic disorders. However, the downstream molecules of Stat5a for inducing Th2 responses are still unknown.In the present research, we attempted to identify the target genes of Stat5a by using ChIP assay. We found that Stat5a was associated in the vicinity of ICOS (inducible T-cell co-stimulator) gene, that the expression of ICOS was enhanced via Stat5a activation in IL-2 stimulated CD4+ T cells, and that the expression of ICOS on follicular helper T cells was induced by Stat5a. These results suggested that Stat5a plays an important role in mounting immune responses in part through the induction of ICOS expression.