title: Coexpression of CCR6 and CD146 (MCAM) is a marker of effector memory T-helper 17 cells.
abstract: Effector memory T (T(EM)) cells are a subpopulation of memory T cells that express receptors mediating migration to inflamed tissues and produce various cytokines. Effector memory T-helper (Th)17 (Th17(EM)) cells are thought to be essential for inflammation in Th17-mediated diseases, but have not been studied in detail. To identify superior surface markers to isolate a homogeneous population of Th17(EM) cells from peripheral blood, CD4(+) T cells were isolated from the peripheral blood of healthy donors based on the expression of CCR7, CCR6 and CD146 using six-color flow cytometry. After 4days of culture in the presence of anti-CD3/28 beads, intracellular cytokines were determined by flow cytometric analysis. To investigate the relevance of Th17(EM) cells in Th17-mediated disease, the frequencies of T(EM) -cell subsets in psoriasis were quantified using six-color flow cytometry. An enzyme-linked immunosorbent assay was performed to confirm the interleukin (IL)-17-producing capacity of T(EM) -cell subsets from the peripheral blood of a patient with psoriasis. CCR6(+) CD146(+) T(EM) (CD4(+) CD45RA(-) CCR7(-)) cells had a greater capacity to produce IL-17 than CCR6(+) CD146(-) or CCR6(-) CD146(+) T(EM) cells. Although the percentage of CCR6(+) CD146(+) cells in T(EM) cells was not significantly different between patients with psoriasis and controls, three of eight patients had a higher percentage of CCR6(+) CD146(+) T(EM) cells than the mean +5 standard deviations of the controls. Coexpression of CCR6 and CD146 is a useful marker for Th17(EM) cells. Increasing the number of CCR6(+) CD146(+) Th17(EM) cells in peripheral blood may facilitate estimation of systemic Th17-cell activity in Th17-mediated diseases.
authors.affiliation: Department of Dermatology, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Taisuke
authors.initials: T
authors.lastname: Kamiyama
authors.forename: Hideaki
authors.initials: H
authors.lastname: Watanabe
authors.forename: Masafumi
authors.initials: M
authors.lastname: Iijima
authors.forename: Akira
authors.initials: A
authors.lastname: Miyazaki
authors.forename: Sanju
authors.initials: S
authors.lastname: Iwamoto
mesh_terms: D000368:Aged; D015415:Biomarkers; D051929:CD146 Antigen / Q000032:analysis / Q000096:biosynthesis / Q000276:immunology; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D020381:Interleukin-17 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000276:immunology*; D054399:Receptors, CCR6 / Q000032:analysis / Q000096:biosynthesis* / Q000276:immunology; D054400:Receptors, CCR7 / Q000032:analysis / Q000276:immunology; D012720:Severity of Illness Index; D058504:Th17 Cells / Q000737:chemistry / Q000276:immunology*
chemical_list: D015415:Biomarkers; C106311:CCR6 protein, human; C515370:CCR7 protein, human; D051929:CD146 Antigen; D018106:CD28 Antigens; D017252:CD3 Complex; D016207:Cytokines; D020381:Interleukin-17; C497902:MCAM protein, human; D054399:Receptors, CCR6; D054400:Receptors, CCR7