Control of TH17 cells occurs in the small intestine

Nature. 2011 Jul 17;475(7357):514-8. doi: 10.1038/nature10228.


Interleukin (IL)-17-producing T helper cells (T(H)17) are a recently identified CD4(+) T cell subset distinct from T helper type 1 (T(H)1) and T helper type 2 (T(H)2) cells. T(H)17 cells can drive antigen-specific autoimmune diseases and are considered the main population of pathogenic T cells driving experimental autoimmune encephalomyelitis (EAE), the mouse model for multiple sclerosis. The factors that are needed for the generation of T(H)17 cells have been well characterized. However, where and how the immune system controls T(H)17 cells in vivo remains unclear. Here, by using a model of tolerance induced by CD3-specific antibody, a model of sepsis and influenza A viral infection (H1N1), we show that pro-inflammatory T(H)17 cells can be redirected to and controlled in the small intestine. T(H)17-specific IL-17A secretion induced expression of the chemokine CCL20 in the small intestine, facilitating the migration of these cells specifically to the small intestine via the CCR6/CCL20 axis. Moreover, we found that T(H)17 cells are controlled by two different mechanisms in the small intestine: first, they are eliminated via the intestinal lumen; second, pro-inflammatory T(H)17 cells simultaneously acquire a regulatory phenotype with in vitro and in vivo immune-suppressive properties (rT(H)17). These results identify mechanisms limiting T(H)17 cell pathogenicity and implicate the gastrointestinal tract as a site for control of T(H)17 cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / immunology
  • Antibodies / pharmacology
  • CD3 Complex / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / transplantation
  • Cell Movement / drug effects
  • Chemokine CCL20 / immunology
  • Disease Models, Animal
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation / immunology
  • Influenza A virus / immunology
  • Interleukin-17 / immunology
  • Intestine, Small / cytology
  • Intestine, Small / immunology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Orthomyxoviridae Infections / immunology
  • Receptors, CCR6 / immunology
  • Sepsis / immunology
  • Staphylococcal Infections / immunology
  • Th17 Cells / immunology*


  • Antibodies
  • CCL20 protein, mouse
  • CCR6 protein, mouse
  • CD3 Complex
  • Chemokine CCL20
  • Il17a protein, mouse
  • Interleukin-17
  • Receptors, CCR6