The roles of CCR6 in migration of Th17 cells and regulation of effector T-cell balance in the gut.
Migration and trafficking receptors of Th17 cells to mucosal tissues have been unclear. We report that Th17 cells preferentially migrate to the intestine and associated lymphoid tissues, and CCR6 is the homing receptor important for Th17 cell migration to certain tissue microenvironments of the intestine such as Peyer's patches and other sites where its ligand CCL20 is expressed. We found the cytokine transforming growth factor-beta1 is required for CCR6 expression whereas IL-2 suppresses it. CCR6-deficient Th17 cells aberrantly migrate to different compartments of the intestine. Surprisingly, administration of CCR6-deficient Th17 cells into severe combined immunodeficiency (SCID) mice led to excessive intestinal inflammation with increased Th1 but decreased Th17 cells and FoxP3(+) T cells. In addition, CCR6 deficiency led to aberrantly widespread effector T cells in the inflamed intestine of the SCID mice. We conclude that CCR6 regulates Th17 cell migration to the gut and effector T-cell balance/distribution in inflamed intestine.
Wang
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Laboratory of Immunology and Hematopoiesis, Department of Comparative Pathobiology, Purdue Cancer Center, Bindley Bioscience Center, Purdue University, West Lafayette, Indiana, USA.
Kang
S G
SG
Lee
J
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Sun
Z
Z
Kim
C H
CH
D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D054418:Chemokine CCL20 / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology / Q000494:pharmacology; D007422:Intestines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D010581:Peyer's Patches / Q000276:immunology; D054399:Receptors, CCR6 / Q000276:immunology* / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D018417:Th1 Cells / Q000276:immunology; D053773:Transforming Growth Factor beta1 / Q000276:immunology / Q000494:pharmacology
C493447:CCL20 protein, mouse; C498126:CCR6 protein, mouse; D054418:Chemokine CCL20; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007376:Interleukin-2; D054399:Receptors, CCR6; D053773:Transforming Growth Factor beta1