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Previously, small proportions of circulating Th1-type CCR5+ and Th2-type CCR3+ cells have been shown in granulomatosis with polyangiitis (GPA). Wondering to what extent CCR4 and CCR6 expression could also be implicated in T cell recruitment to inflamed sites in GPA, we investigated the expression of CCR4 and CCR6 on T cells and its association with T cell diversity and polarization.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods\n<\/jats:title>\n                        <jats:p>Multicolor flow cytometry was used to analyze CCR4, CCR6, and intracellular cytokine expression of T cells from whole blood of GPA-patients (<jats:italic>n<\/jats:italic> = 26) and healthy controls (<jats:italic>n<\/jats:italic> = 20). CCR7 and CD45RA were included for phenotypic characterization.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results\n<\/jats:title>\n                        <jats:p>We found a significant increase in the percentages of circulating CCR4+ and CCR6+ cells within the total CD4+ T cell population in GPA. In contrast, there was no difference in the percentages of CD8+CCR4+ and CD8+CCR6+ T cells between GPA and healthy controls. CCR4 and CCR6 expression was largely confined to central (T<jats:sub>CM<\/jats:sub>) and effector memory T cells (T<jats:sub>EM<\/jats:sub>, T<jats:sub>EMRA<\/jats:sub>). A significant increase in the frequency of CCR4+ and CCR6+ T<jats:sub>EMRA<\/jats:sub> and CCR6+ T<jats:sub>CM<\/jats:sub> was shown in GPA. Of note, we could dissect CCR4 and CCR6 expressing CCR7+CD45RA<jats:sup>med<\/jats:sup> very early memory T cells (T<jats:sub>VEM<\/jats:sub>) from genuine CCR7+CD45RA<jats:sup>high<\/jats:sup> na\u00efve T cells lacking CCR4 and CCR6 expression for peripheral tissue-migration within the CCR7+CD45RA+ compartment. The frequencies of CCR4+ and CCR6+ T<jats:sub>VEM<\/jats:sub> were also significantly increased in GPA. An increased percentage of IL-17+ and IL-22+ cells was detected in the CCR6+ cell subsets and IL-4+ cells in the CRR4+ cell subset when compared with CD4+ cells lacking CCR4 and CCR6 expression.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusions\n<\/jats:title>\n                        <jats:p>Increased frequencies of circulating CCR4+ and CCR6+ memory T cell subsets including hitherto unreported T<jats:sub>VEM<\/jats:sub> suggest persistent T cell activation with the accumulation of CCR4+ and CCR6+ cells in GPA. CCR4 and CCR6 could be involved in the recruitment of T cells including cytokine-producing subsets to inflamed sites in GPA.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/ar3794","type":"journal-article","created":{"date-parts":[[2012,4,10]],"date-time":"2012-04-10T16:14:24Z","timestamp":1334074464000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Increased frequency of CCR4+ and CCR6+ memory T-cells including CCR7+CD45RAmed very early memory cells in granulomatosis with polyangiitis (Wegener's)"],"prefix":"10.1186","volume":"14","author":[{"given":"Ursula","family":"Fagin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silke","family":"Pitann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang L","family":"Gross","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Lamprecht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2012,4,10]]},"reference":[{"key":"3543_CR1","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1016\/S0952-7915(03)00037-2","volume":"15","author":"DL Woodland","year":"2003","unstructured":"Woodland DL, Dutton RW: Heterogeneity of CD4+ and CD8+ T cells. 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