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.
Banerjee
Arnob
A
Abramson Family Cancer Research Institute and Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Schambach
Felix
F
DeJong
Caitlin S
CS
Hammond
Scott M
SM
Reiner
Steven L
SL
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D053633:Receptor, Interferon alpha-beta / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction
D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D053633:Receptor, Interferon alpha-beta; D007371:Interferon-gamma