CCR6 regulates the migration of inflammatory and regulatory T cells.
Th17 and regulatory T (Treg) cells play opposite roles in autoimmune diseases. However, the mechanisms underlying their proper migration to inflammatory tissues are unclear. In this study, we report that these two T cell subsets both express CCR6. CCR6 expression in Th17 cells is regulated by TGF-beta and requires two nuclear receptors, RORalpha and RORgamma. Th17 cells also express the CCR6 ligand CCL20, which is induced synergistically by TGF-beta and IL-6, which requires STAT3, RORgamma and IL-21. Th17 cells, by producing CCL20, promote migration of Th17 and Treg cells in vitro in a CCR6-dependent manner. Lack of CCR6 in Th17 cells reduces the severity of experimental autoimmune encephalomyelitis and Th17 and Treg recruitment into inflammatory tissues. Similarly, CCR6 on Treg cells is also important for their recruitment into inflammatory tissues. Our data indicate an important role of CCR6 in Treg and Th17 cell migration.
Yamazaki
Tomohide
T
Department of Immunology, M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Yang
Xuexian O
XO
Chung
Yeonseok
Y
Fukunaga
Atsushi
A
Nurieva
Roza
R
Pappu
Bhanu
B
Martin-Orozco
Natalia
N
Kang
Hong Soon
HS
Ma
Li
L
Panopoulos
Athanasia D
AD
Craig
Suzanne
S
Watowich
Stephanie S
SS
Jetten
Anton M
AM
Tian
Qiang
Q
Dong
Chen
C
D000595:Amino Acid Sequence; D000818:Animals; D002464:Cell Migration Inhibition / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000235:genetics / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology*; D020381:Interleukin-17 / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D054399:Receptors, CCR6 / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology
C498126:CCR6 protein, mouse; D018836:Inflammation Mediators; D020381:Interleukin-17; D054399:Receptors, CCR6