Interleukin 33 regulates gene expression in intestinal epithelial cells independently of its nuclear localization

Zhengxiang He, Lili Chen, Glaucia C. Furtado, Sergio A. Lira

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Interleukin 33 (IL33) is a cytokine found in the extracellular space (mature IL33) or in the cell nucleus (full-length IL33). Nuclear accumulation of IL33 has been reported in intestinal epithelial cells (IEC) during intestinal inflammation and cancer, but a functional role for this nuclear form remains unclear. To study the role of nuclear IL33 in IEC, we generated transgenic mice expressing full-length IL33 in the intestinal epithelium (Vfl33 mice). Expression of full-length IL33 in the epithelium resulted in accumulation of IL33 protein in the nucleus and secretion of IL33. Over-expression of full-length IL33 by IEC did not promote gut inflammation, but induced expression of genes in the IEC and lamina propria lymphocytes (LPL) that correlated negatively with genes expressed in inflammatory bowel diseases (IBD). Because the IL33 receptor ST2 is expressed by IEC, there was the potential that both the mature and full-length forms could mediate this effect. To specifically interrogate the transcriptional role of nuclear IL33, we intercrossed the Vfl33 mice with ST2- deficient mice. ST2 deficiency completely abrogated the transcriptional effects elicited by IL33 expression, suggesting that the transcriptional effects of IL33 on IEC are mediated by its mature, not its nuclear form.

Original languageEnglish
Pages (from-to)146-153
Number of pages8
StatePublished - Nov 2018


  • IL33
  • Inflammation
  • Inflammatory bowel disease
  • Intestinal epithelial cells
  • RNA-Seq


Dive into the research topics of 'Interleukin 33 regulates gene expression in intestinal epithelial cells independently of its nuclear localization'. Together they form a unique fingerprint.

Cite this