| First Author | Yoshida N | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 12993 | PubMed ID | 27680869 |
| Mgi Jnum | J:242364 | Mgi Id | MGI:5905089 |
| Doi | 10.1038/ncomms12993 | Citation | Yoshida N, et al. (2016) ICER is requisite for Th17 differentiation. Nat Commun 7:12993 |
| abstractText | Inducible cAMP early repressor (ICER) has been described as a transcriptional repressor isoform of the cAMP response element modulator (CREM). Here we report that ICER is predominantly expressed in Th17 cells through the IL-6-STAT3 pathway and binds to the Il17a promoter, where it facilitates the accumulation of the canonical enhancer RORgammat. In vitro differentiation from naive ICER/CREM-deficient CD4+ T cells to Th17 cells is impaired but can be rescued by forced overexpression of ICER. Consistent with a role of Th17 cells in autoimmune and inflammatory diseases, ICER/CREM-deficient B6.lpr mice are protected from developing autoimmunity. Similarly, both anti-glomerular basement membrane-induced glomerulonephritis and experimental encephalomyelitis are attenuated in ICER/CREM-deficient mice compared with their ICER/CREM-sufficient littermates. Importantly, we find ICER overexpressed in CD4+ T cells from patients with systemic lupus erythematosus. Collectively, our findings identify a unique role for ICER, which affects both organ-specific and systemic autoimmunity in a Th17-dependent manner. |
