title: Plasmacytoid dendritic cells in patients with autoimmune thyroid disease.
abstract: BACKGROUND
  Patients with autoimmune thyroid diseases (AITD) show defects in immunoregulatory mechanisms. Herein we assessed the expression of different regulatory receptors in circulating and thyroid dendritic cells (DCs).
  
  
  METHODS
  Peripheral blood samples from 49 patients with Hashimoto's thyroiditis, 35 with Graves' disease, and 34 healthy subjects were studied. Clinical parameters included grades of goiter and ophthalmopathy, thyroid function, and antibody tests. Thyroid tissue samples from 10 AITD patients were also analyzed. Levels of DCs and their expression of different regulatory molecules (IDO, ILT2, ILT3, PSGL-1, PD-L1) were studied. In vitro interferon-α response by plasmacytoid DCs (pDCs) and tryptophan (Trp) metabolites were determined.
  
  
  RESULTS
  Significant low levels of pDCs, but not conventional DCs, were detected in the peripheral blood from AITD patients, mainly in those with severe disease. Furthermore, a diminished expression of ILT3, PSGL-1, and CD69 by peripheral blood pDCs from AITD patients was observed. An increased number of pDCs was found in thyroid tissue, showing a diminished expression of ILT3 and PSGL-1. A lower proportion of IDO+ pDCs, a significant increase in Trp levels, a decrease in the kyneruine/Trp ratio, and an increased in vitro interferon-α response were present in AITD patients. Finally, a significant correlation was found between the in vitro synthesis of IL-10 by stimulated T cells and expression of IDO by pDCs.
  
  
  CONCLUSIONS
  The diminished number of pDCs in the peripheral blood from AITD patients as well as their abnormal phenotype could contribute significantly to the pathogenesis.
authors.affiliation: Service of Endocrinology, Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, 28006 Madrid, Spain. mmarazuela.hlpr@salud.madrid.org
authors.forename: Susanna
authors.initials: S
authors.lastname: Leskela
authors.forename: Ana
authors.initials: A
authors.lastname: Rodríguez-Muñoz
authors.forename: Hortensia
authors.initials: H
authors.lastname: de la Fuente
authors.forename: Nicté
authors.initials: N
authors.lastname: Figueroa-Vega
authors.forename: Pedro
authors.initials: P
authors.lastname: Bonay
authors.forename: Pilar
authors.initials: P
authors.lastname: Martín
authors.forename: Ana
authors.initials: A
authors.lastname: Serrano
authors.forename: Francisco
authors.initials: F
authors.lastname: Sánchez-Madrid
authors.forename: Roberto
authors.initials: R
authors.lastname: González-Amaro
authors.forename: Mónica
authors.initials: M
authors.lastname: Marazuela
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000032:analysis; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006042:Goiter / Q000209:etiology; D006111:Graves Disease / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D050031:Hashimoto Disease / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000097:blood / Q000378:metabolism; D016898:Interferon-alpha / Q000096:biosynthesis / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D013960:Thyroid Function Tests; D013961:Thyroid Gland / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D014364:Tryptophan / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D016207:Cytokines; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D016898:Interferon-alpha; D014364:Tryptophan