Micro-RNA-155 inhibits IFN-gamma signaling in CD4+ T cells.

Micro-RNA (miR) are increasingly recognized as critical regulators of tissue-specific patterns of gene expression. CD4+ T cells lacking miR-155, for example, exhibit bias towards Th2 differentiation, indicating that the absence of individual miR could alter CD4+ T-cell differentiation. We now show that miR-155 is induced upon T-cell activation and that it promotes Th1 differentiation when over-expressed in activated CD4+ T cells. Antagonism of miR-155 leads to induction of IFN-gamma receptor alpha-chain (IFN-gammaRalpha), and a functional miR-155 target site is identified within the 3' untranslated region of IFN-gammaRalpha. These results identify IFN-gammaRalpha as a second miR-155 target in T cells and suggest that miR-155 contributes to Th1 differentiation in CD4+ T cells by inhibiting IFN-gamma signaling.