| Regulatory T (Treg) cells play a critical role in maintaining self-tolerance and controlling the magnitude of physiologic immune response. We were interested to determine whether Treg differentiation and/or suppressive activity are regulated by microRNAs (miRNAs). miRNAs are short (~22 nt) noncoding RNAs, expressed from endogenous genes, and are the products of sequential processing of primary RNA polymerase II transcripts mediated by two RNase III enzymes. MiR17-92 overexpression in hematopoietic cells has been reported by Rajewsky etc. to result in an autoimmune syndrome. However, the exact mechanism and the role of T cell regulation haven't been well studied. Here, we showed the first time that one miRAN of the miR17-92 cluster, miR-17, regulates the suppression function of Treg. We identify a gene target of miR-17, Eos, which regulates Treg through Foxp3-mediated gene suppression. IL-6 actively affects Eos expression through miR-17, thus downmodulating Treg suppression function and providing Treg with partial effector activity via de-repression of cytokine genes. In addition, mir17-92 cluster knockdown can mitigate experimental autoimmune encephalomyelitis (EAE) in mice. Our studies suggest that miR-17 modulates Treg cells function by targeting Eos, which revealed future therapeutic potential of miR-17 manipulation in cancer or autoimmune disease. |
