title: Characterization of gliadin-specific Th17 cells from the mucosa of celiac disease patients.
abstract: OBJECTIVE
  Celiac disease (CD) is a disorder characterized by a deregulated immune response to ingested wheat gluten and related cereal proteins in susceptible individuals. It has been considered that the onset of CD is mediated by a skewed Th1 response. However, the participation of Th17 cells in the pathogenesis of the disease, a key cell population in other autoimmune disorders, has not been studied in detail. We have investigated the presence of Th17 cells in the mucosa of active CD patients and their functional implications in the pathogenesis of the disease.
  
  
  METHODS
  T cells obtained from duodenum biopsies from 15 untreated patients and 11 control individuals were characterized by flow cytometry, immunoassays, and real-time PCR.
  
  
  RESULTS
  We found gliadin-specific CD4(+) interleukin (IL)-17A-producing T cells in the mucosa of CD patients with a phenotype consisting of TCR (T-cell receptor)αβ(+) CD45RO(+) CD161(+) CCR6(+) (C-C chemokine receptor type 6) and IL-23R(+). Functional analysis showed that Th17 cells from CD patients are different from those of control individuals in terms of cytokines production. Th17 cells from CD patients, but not from controls, simultaneously express transforming growth factor-β (TGFβ). Th17 CD cells also produce interferon-γ (IFNγ), IL-21, and IL-22. The analysis of the transcription factors revealed a high expression of interferon regulatory factor-4 as a feature of gliadin-specific cells from CD patients with respect to controls.
  
  
  CONCLUSIONS
  Gliadin-specific Th17 cells are present in the mucosa of CD patients having a dual role in the pathogenesis of the disease as they produce proinflammatory cytokines (such as IL-17, IFNγ, IL-21), mucosa-protective IL-22, and regulatory TGFβ, which actively modulates IL-17A production by T cells in the celiac mucosa.
authors.affiliation: Unidad de Inmunología, Facultad de Medicina, Universidad de Córdoba, Córdoba, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Fernández
authors.forename: Ignacio J
authors.initials: IJ
authors.lastname: Molina
authors.forename: Pilar
authors.initials: P
authors.lastname: Romero
authors.forename: Rafael
authors.initials: R
authors.lastname: González
authors.forename: José
authors.initials: J
authors.lastname: Peña
authors.forename: Francisco
authors.initials: F
authors.lastname: Sánchez
authors.forename: Fernanda R
authors.initials: FR
authors.lastname: Reynoso
authors.forename: Juan L
authors.initials: JL
authors.lastname: Pérez-Navero
authors.forename: Orlando
authors.initials: O
authors.lastname: Estevez
authors.forename: Consuelo
authors.initials: C
authors.lastname: Ortega
authors.forename: Manuel
authors.initials: M
authors.lastname: Santamaría
mesh_terms: D000293:Adolescent; D002446:Celiac Disease / Q000175:diagnosis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D005903:Gliadin / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007118:Immunoassay; D007249:Inflammation / Q000276:immunology; D050835:Interferon Regulatory Factors / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism; D016133:Polymerase Chain Reaction; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D000097043:Interleukin-22; D000098546:Interleukin-21; D000099218:Interferon Regulatory Factor-4
chemical_list: D016207:Cytokines; D005903:Gliadin; D050835:Interferon Regulatory Factors; D007371:Interferon-gamma; D020381:Interleukin-17; D007378:Interleukins; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D016212:Transforming Growth Factor beta; D000097043:Interleukin-22; D000098546:Interleukin-21; D000099218:Interferon Regulatory Factor-4; C539900:RORC protein, human