| First Author | Hewitson JP | Year | 2019 |
| Journal | EMBO Rep | Volume | 20 |
| Issue | 4 | PubMed ID | 30833344 |
| Mgi Jnum | J:273201 | Mgi Id | MGI:6286567 |
| Doi | 10.15252/embr.201846620 | Citation | Hewitson JP, et al. (2019) miR-132 suppresses transcription of ribosomal proteins to promote protective Th1 immunity. EMBO Rep 20(4) |
| abstractText | Determining the mechanisms that distinguish protective immunity from pathological chronic inflammation remains a fundamental challenge. miR-132 has been shown to play largely immunoregulatory roles in immunity; however, its role in CD4(+) T cell function is poorly understood. Here, we show that CD4(+) T cells express high levels of miR-132 and that T cell activation leads to miR-132 up-regulation. The transcriptomic hallmark of splenic CD4(+) T cells lacking the miR-132/212 cluster during chronic infection is an increase in mRNA levels of ribosomal protein (RP) genes. BTAF1, a co-factor of B-TFIID and novel miR-132/212-3p target, and p300 contribute towards miR-132/212-mediated regulation of RP transcription. Following infection with Leishmania donovani, miR-132 (-/-) CD4(+) T cells display enhanced expression of IL-10 and decreased IFNgamma. This is associated with reduced hepatosplenomegaly and enhanced pathogen load. The enhanced IL-10 expression in miR-132 (-/-) Th1 cells is recapitulated in vitro following treatment with phenylephrine, a drug reported to promote ribosome synthesis. Our results uncover that miR-132/212-mediated regulation of RP expression is critical for optimal CD4(+) T cell activation and protective immunity against pathogens. |
