ICER is requisite for Th17 differentiation

Nobuya Yoshida, Denis Comte, Masayuki Mizui, Kotaro Otomo, Florencia Rosetti, Tanya N. Mayadas, José C. Crispín, Sean J. Bradley, Tomohiro Koga, Michihito Kono, Maria P. Karampetsou, Vasileios C. Kyttaris, Klaus Tenbrock, George C. Tsokos

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22 Citations (Scopus)

Abstract

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 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.

Original languageEnglish
Article number12993
JournalNature communications
Volume7
DOIs
Publication statusPublished - 2016 Sep 29

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Yoshida, N., Comte, D., Mizui, M., Otomo, K., Rosetti, F., Mayadas, T. N., Crispín, J. C., Bradley, S. J., Koga, T., Kono, M., Karampetsou, M. P., Kyttaris, V. C., Tenbrock, K., & Tsokos, G. C. (2016). ICER is requisite for Th17 differentiation. Nature communications, 7, [12993]. https://doi.org/10.1038/ncomms12993