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

研究成果: Article査読

33 被引用数 (Scopus)

抄録

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.

本文言語English
論文番号12993
ジャーナルNature communications
7
DOI
出版ステータスPublished - 2016 9 29
外部発表はい

ASJC Scopus subject areas

  • 化学 (全般)
  • 生化学、遺伝学、分子生物学(全般)
  • 物理学および天文学(全般)

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