It has been established that there is an enrichment of T helper 17 (T_H17) cells in the intestine, but the molecular basis of this tissue tropism is not fully understood. Now, a study published in Mucosal Immunology shows that the expression of CC-chemokine receptor 6 (CCR6) by T_H17 cells is required for their migration to specific sites in the intestine and that this receptor has a role in preventing excessive intestinal inflammation.

The authors first determined the exact distribution of T_H17 cells in different mouse tissues and found that most T_H17 cells were localized at the small and large intestine, Peyer's patches and liver. T_H17 cells that were generated in vitro and transferred to naive mice readily migrated to the large intestine, Peyer's patches and peritoneal cavity, but migrated less efficiently to peripheral lymph nodes. This was in contrast to in vitro-generated FOXP3⁺ (forkhead box P3) T cells, which preferentially migrated to peripheral lymph nodes and bone marrow.

T_H17 cells from different tissues were found to heterogeneously express several trafficking receptors; however, CCR6 was the only receptor that was expressed by all T_H17 cells examined (including in vitro-generated T_H17 cells). Furthermore, the ability of in vitro-generated Ccr6^-/- T_H17 cells to migrate to the Peyer's patches and small intestine following their transfer into wild-type mice was significantly decreased compared with wild-type T_H17 cells, indicating a role for CCR6 in the homing of T_H17 cells to the intestine.

The authors then compared the extent of T-cell-induced colitis in SCID (severe combined immunodeficiency) mice that received wild-type or Ccr6^-/- T_H17 cells. Surprisingly, mice that received Ccr6^-/- T_H17 cells showed greater signs of intestinal inflammation than mice that received wild-type T_H17 cells. In addition, the intestine of mice that received Ccr6^-/- T_H17 cells contained fewer T_H17 cells but more T_H1 cells than the intestine of mice that received wild-type T_H17 cells. This suggests that T_H17 cells can become inflammatory T_H1 cells in a process that is accelerated in the absence of CCR6.

Together, these results suggest that CCR6 is required for the homing of T_H17 cells to specific sites in the intestine and is involved in regulating the effector T-cell balance in the inflamed intestine.

Author: Olive Leavy - Copyright © 2009 Nature Publishing Group, a division of MacMillan Publishers Limited; used with permission