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Elevated frequency of TLR<jats:sup>+<\/jats:sup>T-cells has been associated with neurological inflammatory disorders. As T-cells and B-cells are found in CCM lesions, the objective of the present study was to evaluate the cytokine profile of T-cells expressing TLR2 and TLR4, as well as B-cell subsets, in asymptomatic (CCM<jats:sub>Asympt<\/jats:sub>) and symptomatic (CCM<jats:sub>Sympt<\/jats:sub>) patients.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>For our study, the cytokine profile from TLR2<jats:sup>+<\/jats:sup>\u00a0and TLR4<jats:sup>+<\/jats:sup>\u00a0T-cell and B-cell subsets in CCM<jats:sub>Asympt<\/jats:sub> and CCM<jats:sub>Sympt<\/jats:sub>\u00a0patients was investigated using flow cytometry and ELISA. T-cells were stimulated in vitro with anti-CD3\/anti-CD28 beads or TLR2 (Pam3C) and TLR4 (LPS) ligands.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>CCM<jats:sub>Symptc<\/jats:sub>\u00a0patients presented a higher frequency of TLR4<jats:sup>+<\/jats:sup>(CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup>) T-cells and greater density of TLR4 expression on these cells. With regard to the cytokine profile, the percentage of TLR2<jats:sup>+<\/jats:sup> and TLR4<jats:sup>+<\/jats:sup> Th17 cells was higher in CCM<jats:sub>Sympt<\/jats:sub> patients. In addition, an elevated proportion of TLR4<jats:sup>+\u00a0<\/jats:sup>Tc-1 cells, as well as Tc-17 and Th17.1 cells expressing TLR2 and TLR4, was observed in the symptomatic patients. By contrast, the percentage of TLR4<jats:sup>+<\/jats:sup> IL-10<jats:sup>+<\/jats:sup>CD4<jats:sup>+<\/jats:sup>\u00a0T cells was higher in the CCM<jats:sub>Asympt<\/jats:sub>\u00a0group. Both Pam3C and LPS were more able to elevate the frequency of IL-6<jats:sup>+<\/jats:sup>CD4<jats:sup>+<\/jats:sup>T cells and Th17.1 cells in CCM<jats:sub>Sympt<\/jats:sub>\u00a0cell cultures. Furthermore, in comparison with asymptomatic patients, purified T-cells from the CCM<jats:sub>Sympt<\/jats:sub> group released higher levels of Th17-related cytokines in response to Pam3C and, mainly, LPS, as well as after activation via TCR\/CD28. Concerning the B-cell subsets, a higher frequency of memory and memory activated B-cells\u00a0was observed in CCM<jats:sub>Sympt<\/jats:sub> patients.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Our findings reveal an increase in circulating Th17\/Tc-17 cell subsets expressing functional TLR2 and, mainly, TLR4 molecules, associated with an increase in memory B-cell subsets in CCM patients with clinical activity of the disease.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12974-022-02385-2","type":"journal-article","created":{"date-parts":[[2022,2,2]],"date-time":"2022-02-02T08:03:39Z","timestamp":1643789019000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Elevated proportion of TLR2- and TLR4-expressing Th17-like cells and activated memory B cells was associated with clinical activity of cerebral cavernous malformations"],"prefix":"10.1186","volume":"19","author":[{"given":"Camilla","family":"Castro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo A. 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