Control of [T.sub.H]17 cells occurs in the small intestine

[T.sub.H]17 cells have been associated with the pathogenesis of several chronic inflammatory disorders, including rheumatoid arthritis and multiple sclerosis (2,7). To study the cellular and molecular mechanisms that control pathogenicity [...]
Interleukin (IL)-17-producing T helper cells ([T.sub.H]17) are a recently identified [CD4.sup.+] T cell subset distinct from T helper type 1 ([T.sub.H]1) and T helper type 2 ([T.sub.H]2) cells (1). [T.sub.H]17 cells can drive antigenspecific autoimmune diseases and are considered the main population of pathogenic T cells driving experimental autoimmune encephalomyelitis (EAE) (2), the mouse model for multiple sclerosis. The factors that are needed for the generation of [T.sub.H]17 cells have been well characterized (3-6). However, where and how the immune system controls [T.sub.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.sub.H]17 cells can be redirected to and controlled in the small intestine. [T.sub.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.sub.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.sub.H]17 cells simultaneously acquire a regulatory phenotype with invitro and invivoimmune-suppressive properties (r[T.sub.H]17). These results identify mechanisms limiting [T.sub.H]17 cell pathogenicity and implicate the gastrointestinal tract as a site for control of [T.sub.H]17 cells.