IL-17C regulates the innate immune function of epithelial cells in an autocrine manner

Nat Immunol. 2011 Oct 12;12(12):1159-66. doi: 10.1038/ni.2156.


Interleukin 17C (IL-17C) is a member of the IL-17 family that is selectively induced in epithelia by bacterial challenge and inflammatory stimuli. Here we show that IL-17C functioned in a unique autocrine manner, binding to a receptor complex consisting of the receptors IL-17RA and IL-17RE, which was preferentially expressed on tissue epithelial cells. IL-17C stimulated epithelial inflammatory responses, including the expression of proinflammatory cytokines, chemokines and antimicrobial peptides, which were similar to those induced by IL-17A and IL-17F. However, IL-17C was produced by distinct cellular sources, such as epithelial cells, in contrast to IL-17A, which was produced mainly by leukocytes, especially those of the T(H)17 subset of helper T cells. Whereas IL-17C promoted inflammation in an imiquimod-induced skin-inflammation model, it exerted protective functions in dextran sodium sulfate-induced colitis. Thus, IL-17C is an essential autocrine cytokine that regulates innate epithelial immune responses.

MeSH terms

  • Animals
  • Autocrine Communication*
  • Cell Line
  • Colitis / chemically induced
  • Colitis / metabolism
  • Colitis / pathology
  • Epithelial Cells / immunology*
  • Epithelial Cells / metabolism
  • Gene Expression Profiling
  • HEK293 Cells
  • Humans
  • Immunity, Innate / immunology*
  • Inflammation / immunology
  • Inflammation / microbiology
  • Interleukin-17 / metabolism*
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / microbiology
  • Leukocytes / immunology
  • Leukocytes / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phenotype
  • Protein Binding
  • Receptors, Interleukin-17 / metabolism
  • Respiratory Mucosa / immunology
  • Respiratory Mucosa / metabolism
  • Respiratory Mucosa / microbiology
  • Signal Transduction
  • Skin / immunology
  • Skin / metabolism
  • Skin / pathology


  • Interleukin-17
  • Receptors, Interleukin-17

Associated data

  • GEO/GSE32620