Alterations in the microbiota drive interleukin-17C production from intestinal epithelial cells to promote tumorigenesis

Immunity. 2014 Jan 16;40(1):140-52. doi: 10.1016/j.immuni.2013.11.018. Epub 2014 Jan 9.


Although the microbiota has been shown to drive production of interleukin-17A (IL-17A) from T helper 17 cells to promote cell proliferation and tumor growth in colorectal cancer, the molecular mechanisms for microbiota-mediated regulation of tumorigenesis are largely unknown. Here, we found that the innate-like cytokine IL-17C was upregulated in human colorectal cancers and in mouse intestinal tumor models. Alterations in the microbiota drove IL-17C upregulation specifically in intestinal epithelial cells (IECs) through Toll-like receptor (TLR)-MyD88-dependent signaling during intestinal tumorigenesis. Microbiota-driven IL-17C induced Bcl-2 and Bcl-xL expression in IECs in an autocrine manner to promote cell survival and tumorigenesis in both chemically induced and spontaneous intestinal tumor models. Thus, IL-17C promotes cancer development by increasing IEC survival, and the microbiota can mediate cancer pathogenesis through regulation of IL-17C.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autocrine Communication
  • Carcinogenesis / immunology*
  • Cell Survival
  • Cells, Cultured
  • Colonic Neoplasms / immunology*
  • Colonic Neoplasms / microbiology
  • Disease Models, Animal
  • Humans
  • Interleukin-17 / genetics
  • Interleukin-17 / metabolism*
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / microbiology
  • Mice
  • Mice, Knockout
  • Microbiota / immunology*
  • Myeloid Differentiation Factor 88 / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Signal Transduction
  • Up-Regulation
  • bcl-X Protein / genetics
  • bcl-X Protein / metabolism


  • Interleukin-17
  • Myeloid Differentiation Factor 88
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-X Protein