Coexpression of CCR6 and CD146 (MCAM) is a marker of effector memory T-helper 17 cells

Effector memory T (TEM) 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 (Th17EM) 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 Th17EM 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 4 days of culture in the presence of anti-CD3/28 beads, intracellular cytokines were determined by flow cytometric analysis. To investigate the relevance of Th17EM cells in Th17-mediated disease, the frequencies of TEM-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 TEM-cell subsets from the peripheral blood of a patient with psoriasis. CCR6+CD146+ TEM (CD4+CD45RA-CCR7-) cells had a greater capacity to produce IL-17 than CCR6+CD146- or CCR6-CD146+ TEM cells. Although the percentage of CCR6+CD146+ cells in TEM cells was not significantly different between patients with psoriasis and controls, three of eight patients had a higher percentage of CCR6+CD146+ TEM cells than the mean +5 standard deviations of the controls. Coexpression of CCR6 and CD146 is a useful marker for Th17EM cells. Increasing the number of CCR6+CD146+ Th17EM cells in peripheral blood may facilitate estimation of systemic Th17-cell activity in Th17-mediated diseases.