title: Circulating Microvesicles Regulate Treg and Th17 Differentiation in Human Autoimmune Thyroid Disorders.
abstract: BACKGROUND
  Microvesicles (MVs) are emerging as important contributors to the development of inflammatory and autoimmune diseases. MVs can mediate immune modulation carrying genetic information, including microRNAs that can be transferred between cells.
  
  
  METHODS
  We determined the plasma levels of annexin-V+ MVs derived from different immune cells and platelets in patients with autoimmune thyroid diseases (AITDs) and in healthy controls. T lymphocyte polarization assays were performed in the presence of MVs to evaluate their effect in T regulatory and T helper 17 cells differentiation. microRNA content into plasma MVs and their corresponding mRNA targets were evaluated by RT-PCR.
  
  
  RESULTS
  The percentage of platelet-derived MVs (CD41a+) was significantly increased in plasma samples from AITD patients compared with healthy controls. In contrast, patients with AITD showed a lower percentage of leukocyte and endothelial cell-derived MVs compared with controls. In addition, functional assays showed that MVs from AITD patients inhibited the in vitro differentiation of Foxp3+ T regulatory cells (11.35% vs 4.40%, P = .01) and induced the expression of interferon-γ by CD4+ lymphocytes (10.91% vs 13.99%, P = .01) as well as the differentiation of T helper 17 pathogenic (IL-17+interferon-γ+) cells (1.98% vs 5.13%, P = .03). Furthermore, in AITD patients, whereas miR-146a and miR-155 were increased in circulating MVs, their targets IL-8 and SMAD4 were decreased in peripheral blood mononuclear cells.
  
  
  CONCLUSIONS
  Our data indicate that circulating MVs seem to have a relevant role in the modulation of the inflammatory response observed in AITD.
authors.affiliation: Department of Endocrinology (A.R.-M., R.-M.-H., A.M.R.-L., A.S.-S., M.M.), Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa, Universidad Autónoma de Madrid, 28006 Madrid, Spain; Department of Immunology (F.S.-M., H.d.l.F.), Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa, Universidad Autónoma de Madrid, Centro Nacional de Investigaciones Cardiovasculares, 28029 Madrid, Spain; and Department of Immunology (R.G.-A.), School of Medicine, Universidad Autónoma de San Luis Potosí, 78210 San Luis Potosí, SLP, México.
authors.forename: Ana
authors.initials: A
authors.lastname: Rodríguez-Muñoz
authors.affiliation: Department of Endocrinology (A.R.-M., R.-M.-H., A.M.R.-L., A.S.-S., M.M.), Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa, Universidad Autónoma de Madrid, 28006 Madrid, Spain; Department of Immunology (F.S.-M., H.d.l.F.), Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa, Universidad Autónoma de Madrid, Centro Nacional de Investigaciones Cardiovasculares, 28029 Madrid, Spain; and Department of Immunology (R.G.-A.), School of Medicine, Universidad Autónoma de San Luis Potosí, 78210 San Luis Potosí, SLP, México.
authors.forename: Rebeca
authors.initials: R
authors.lastname: Martínez-Hernández
authors.affiliation: Department of Endocrinology (A.R.-M., R.-M.-H., A.M.R.-L., A.S.-S., M.M.), Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa, Universidad Autónoma de Madrid, 28006 Madrid, Spain; Department of Immunology (F.S.-M., H.d.l.F.), Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa, Universidad Autónoma de Madrid, Centro Nacional de Investigaciones Cardiovasculares, 28029 Madrid, Spain; and Department of Immunology (R.G.-A.), School of Medicine, Universidad Autónoma de San Luis Potosí, 78210 San Luis Potosí, SLP, México.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Ramos-Leví
authors.affiliation: Department of Endocrinology (A.R.-M., R.-M.-H., A.M.R.-L., A.S.-S., M.M.), Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa, Universidad Autónoma de Madrid, 28006 Madrid, Spain; Department of Immunology (F.S.-M., H.d.l.F.), Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa, Universidad Autónoma de Madrid, Centro Nacional de Investigaciones Cardiovasculares, 28029 Madrid, Spain; and Department of Immunology (R.G.-A.), School of Medicine, Universidad Autónoma de San Luis Potosí, 78210 San Luis Potosí, SLP, México.
authors.forename: Ana
authors.initials: A
authors.lastname: Serrano-Somavilla
authors.affiliation: Department of Endocrinology (A.R.-M., R.-M.-H., A.M.R.-L., A.S.-S., M.M.), Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa, Universidad Autónoma de Madrid, 28006 Madrid, Spain; Department of Immunology (F.S.-M., H.d.l.F.), Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa, Universidad Autónoma de Madrid, Centro Nacional de Investigaciones Cardiovasculares, 28029 Madrid, Spain; and Department of Immunology (R.G.-A.), School of Medicine, Universidad Autónoma de San Luis Potosí, 78210 San Luis Potosí, SLP, México.
authors.forename: Roberto
authors.initials: R
authors.lastname: González-Amaro
authors.affiliation: Department of Endocrinology (A.R.-M., R.-M.-H., A.M.R.-L., A.S.-S., M.M.), Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa, Universidad Autónoma de Madrid, 28006 Madrid, Spain; Department of Immunology (F.S.-M., H.d.l.F.), Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa, Universidad Autónoma de Madrid, Centro Nacional de Investigaciones Cardiovasculares, 28029 Madrid, Spain; and Department of Immunology (R.G.-A.), School of Medicine, Universidad Autónoma de San Luis Potosí, 78210 San Luis Potosí, SLP, México.
authors.forename: Francisco
authors.initials: F
authors.lastname: Sánchez-Madrid
authors.affiliation: Department of Endocrinology (A.R.-M., R.-M.-H., A.M.R.-L., A.S.-S., M.M.), Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa, Universidad Autónoma de Madrid, 28006 Madrid, Spain; Department of Immunology (F.S.-M., H.d.l.F.), Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa, Universidad Autónoma de Madrid, Centro Nacional de Investigaciones Cardiovasculares, 28029 Madrid, Spain; and Department of Immunology (R.G.-A.), School of Medicine, Universidad Autónoma de San Luis Potosí, 78210 San Luis Potosí, SLP, México.
authors.forename: Hortensia
authors.initials: H
authors.lastname: de la Fuente
authors.affiliation: Department of Endocrinology (A.R.-M., R.-M.-H., A.M.R.-L., A.S.-S., M.M.), Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa, Universidad Autónoma de Madrid, 28006 Madrid, Spain; Department of Immunology (F.S.-M., H.d.l.F.), Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa, Universidad Autónoma de Madrid, Centro Nacional de Investigaciones Cardiovasculares, 28029 Madrid, Spain; and Department of Immunology (R.G.-A.), School of Medicine, Universidad Autónoma de San Luis Potosí, 78210 San Luis Potosí, SLP, México.
authors.forename: Mónica
authors.initials: M
authors.lastname: Marazuela
mesh_terms: D017209:Apoptosis; D001792:Blood Platelets / Q000737:chemistry; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D002454:Cell Differentiation; D022162:Cytoplasmic Vesicles / Q000473:pathology*; D005434:Flow Cytometry; D006801:Humans; D016209:Interleukin-8 / Q000097:blood; D035683:MicroRNAs / Q000097:blood / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000097:blood; D051901:Smad4 Protein / Q000097:blood; D050378:T-Lymphocytes, Regulatory / Q000473:pathology*; D058504:Th17 Cells / Q000473:pathology*; D013967:Thyroiditis, Autoimmune / Q000473:pathology*
chemical_list: C508606:CXCL8 protein, human; D016209:Interleukin-8; C542542:MIRN146 microRNA, human; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C497796:SMAD4 protein, human; D051901:Smad4 Protein