title: CCR6 regulates the migration of inflammatory and regulatory T cells.
abstract: 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.
authors.affiliation: Department of Immunology, M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Tomohide
authors.initials: T
authors.lastname: Yamazaki
authors.forename: Xuexian O
authors.initials: XO
authors.lastname: Yang
authors.forename: Yeonseok
authors.initials: Y
authors.lastname: Chung
authors.forename: Atsushi
authors.initials: A
authors.lastname: Fukunaga
authors.forename: Roza
authors.initials: R
authors.lastname: Nurieva
authors.forename: Bhanu
authors.initials: B
authors.lastname: Pappu
authors.forename: Natalia
authors.initials: N
authors.lastname: Martin-Orozco
authors.forename: Hong Soon
authors.initials: HS
authors.lastname: Kang
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.forename: Athanasia D
authors.initials: AD
authors.lastname: Panopoulos
authors.forename: Suzanne
authors.initials: S
authors.lastname: Craig
authors.forename: Stephanie S
authors.initials: SS
authors.lastname: Watowich
authors.forename: Anton M
authors.initials: AM
authors.lastname: Jetten
authors.forename: Qiang
authors.initials: Q
authors.lastname: Tian
authors.forename: Chen
authors.initials: C
authors.lastname: Dong
mesh_terms: 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
chemical_list: C498126:CCR6 protein, mouse; D018836:Inflammation Mediators; D020381:Interleukin-17; D054399:Receptors, CCR6