This study shows that interleukin (IL)-17-producing T helper type 17 (Th17) cells predominantly express CC chemokine receptor (CCR)6 in an animal model of rheumatoid arthritis (RA). Th17 cells induced in vivo in normal mice via homeostatic proliferation similarly express CCR6, whereas those inducible in vitro by transforming growth factor β and IL-6 additionally need IL-1 and neutralization of interferon (IFN) γ and IL-4 for CCR6 expression. Forced expression of RORγt, a key transcription factor for Th17 cell differentiation, induces not only IL-17 but also CCR6 in naive T cells. Furthermore, Th17 cells produce CCL20, the known ligand for CCR6. Synoviocytes from arthritic joints of mice and humans also produce a large amount of CCL20, with a significant correlation (P = 0.014) between the amounts of IL-17 and CCL20 in RA joints. The CCL20 production by synoviocytes is augmented in vitro by IL-1β, IL-17, or tumor necrosis factor α, and is suppressed by IFN-γ or IL-4. Administration of blocking anti-CCR6 monoclonal antibody substantially inhibits mouse arthritis. Thus, the joint cytokine milieu formed by T cells and synovial cells controls the production of CCL20 and, consequently, the recruitment of CCR6+ arthritogenic Th17 cells to the inflamed joints. These results indicate that CCR6 expression contributes to Th17 cell function in autoimmune disease, especially in autoimmune arthritis such as RA. Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease that primarily affects multiple joints. Autoimmune CD4+ T cells are required for the progression of RA, especially in an initial phase of the disease. Recent studies with animal models have suggested that CD4+ T cells secreting IL-17 (IL-17A), called Th17 cells, may play a key role in the progression of RA as well as multiple sclerosis. Hindering the development of Th17 cells or blocking IL-17 activity indeed inhibits autoimmune pathology in these models. A particular cytokine milieu contributes to this preferential differentiation of naive self-reactive T cells to Th17 effector cells. In addition, the transcription factor RORγt specifically controls Th17 cell differentiation, indicating that Th17 cells form a T cell lineage distinct from Th1 or Th2 cells. To further analyze the roles of Th17 cells in autoimmune disease, we have searched for cell-surface molecules that are specifically expressed in Th17 cells and are crucial for their functions, such as their migration to inflamed joints in RA. The SKG strain of miceThis study shows that interleukin (IL)-17-producing T helper type 17 (Th17) cells predominantly express CC chemokine receptor (CCR)6 in an animal model of rheumatoid arthritis (RA). Th17 cells induced in vivo in normal mice via homeostatic proliferation similarly express CCR6, whereas those inducible in vitro by transforming growth factor β and IL-6 additionally need IL-1 and neutralization of interferon (IFN) γ and IL-4 for CCR6 expression. Forced expression of RORγt, a key transcription factor for Th17 cell differentiation, induces not only IL-17 but also CCR6 in naive T cells. Furthermore, Th17 cells produce CCL20, the known ligand for CCR6. Synoviocytes from arthritic joints of mice and humans also produce a large amount of CCL20, with a significant correlation (P = 0.014) between the amounts of IL-17 and CCL20 in RA joints. The CCL20 production by synoviocytes is augmented in vitro by IL-1β, IL-17, or tumor necrosis factor α, and is suppressed by IFN-γ or IL-4. Administration of blocking anti-CCR6 monoclonal antibody substantially inhibits mouse arthritis. Thus, the joint cytokine milieu formed by T cells and synovial cells controls the production of CCL20 and, consequently, the recruitment of CCR6+ arthritogenic Th17 cells to the inflamed joints. These results indicate that CCR6 expression contributes to Th17 cell function in autoimmune disease, especially in autoimmune arthritis such as RA. Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease that primarily affects multiple joints. Autoimmune CD4+ T cells are required for the progression of RA, especially in an initial phase of the disease. Recent studies with animal models have suggested that CD4+ T cells secreting IL-17 (IL-17A), called Th17 cells, may play a key role in the progression of RA as well as multiple sclerosis. Hindering the development of Th17 cells or blocking IL-17 activity indeed inhibits autoimmune pathology in these models. A particular cytokine milieu contributes to this preferential differentiation of naive self-reactive T cells to Th17 effector cells. In addition, the transcription factor RORγt specifically controls Th17 cell differentiation, indicating that Th17 cells form a T cell lineage distinct from Th1 or Th2 cells. To further analyze the roles of Th17 cells in autoimmune disease, we have searched for cell-surface molecules that are specifically expressed in Th17 cells and are crucial for their functions, such as their migration to inflamed joints in RA. The SKG strain of mice