Yoshida, NobuyaComte, DenisMizui, MasayukiOtomo, KotaroRosetti, FlorenciaMayadas, TanyaCrispín, José C.Bradley, Sean J.Koga, TomohiroKono, MichihitoKarampetsou, Maria P.Kyttaris, VasileiosTenbrock, KlausTsokos, George2016-11-182016Yoshida, N., D. Comte, M. Mizui, K. Otomo, F. Rosetti, T. N. Mayadas, J. C. Crispín, et al. 2016. “ICER is requisite for Th17 differentiation.” Nature Communications 7 (1): 12993. doi:10.1038/ncomms12993. http://dx.doi.org/10.1038/ncomms12993.2041-1723http://nrs.harvard.edu/urn-3:HUL.InstRepos:29408151Inducible 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 RORγt. 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.en-USJournal Article2016-11-1810.1038/ncomms12993