Flagellin stimulation suppresses IL-7 secretion of intestinal epithelial cells

Cytokine. 2008 Oct;44(1):57-64. doi: 10.1016/j.cyto.2008.06.004. Epub 2008 Jul 25.

Abstract

IL-7 is a cytokine, which regulates development, maintenance and proliferation of T lymphocytes within the human immune system. Production of IL-7 is observed in a sterile environment such as thymus or bone marrow. However, it is also known that intestinal epithelial cells (IECs) residing in close contact with numerous bacterial stimuli also produce IL-7. Here we show that secretion of IL-7 by IECs is significantly suppressed upon stimulation by various bacterial components, including flagellin. Analysis of the intracellular mechanism by which flagellin regulates IL-7 production revealed that flagellin down-regulates expression of the two major transcripts encoding IL-7. Surprisingly, such function of flagellin was independent from the known transcriptional regulation of the IL-7 gene, as no significant change was observed in the transcriptional activity regulated by the previously identified promoter region. As the stability of IL-7 mRNA also remained unchanged upon flagellin stimulation, results suggested the possible involvement of a yet unknown transcriptional regulation of the IL-7 gene. These results describe a novel regulation of IL-7 production by bacterial stimuli, presumably mediated via Toll-like receptors. The present system might contribute to regulate the local lymphocyte pool, in response to the gut luminal or sub-mucosal bacterial abundance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Colonic Neoplasms
  • Down-Regulation
  • Flagellin / pharmacology*
  • Humans
  • Interleukin-7 / antagonists & inhibitors
  • Interleukin-7 / metabolism*
  • Intestinal Mucosa / cytology
  • RNA, Messenger / metabolism

Substances

  • IL7 protein, human
  • Interleukin-7
  • RNA, Messenger
  • Flagellin