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Expression of CCR6 and CXCR6 by Gut-Derived CD4+/CD8α+ T-Regulatory Cells, Which Are Decreased in Blood Samples From Patients With Inflammatory Bowel Diseases.
Godefroy, Emmanuelle; Alameddine, Joudy; Montassier, Emmanuel; Mathé, Justine; Desfrançois-Noël, Juliette; Marec, Nadège; Bossard, Céline; Jarry, Anne; Bridonneau, Chantal; Le Roy, Amandine; Sarrabayrouse, Guillaume; Kerdreux, Elise; Bourreille, Arnaud; Sokol, Harry; Jotereau, Francine; Altare, Frédéric.
Afiliación
  • Godefroy E; CRCINA, INSERM, University of Nantes, University of Angers, Nantes, France.
  • Alameddine J; CRCINA, INSERM, University of Nantes, University of Angers, Nantes, France.
  • Montassier E; MiHAR Lab, Institut de Recherche en Santé 2, Université de Nantes, Nantes, France; Emergency Department, Centre Hospitalier Universitaire de Nantes, Nantes, France.
  • Mathé J; CRCINA, INSERM, University of Nantes, University of Angers, Nantes, France.
  • Desfrançois-Noël J; CytoCell, IRS-UN, Nantes, France.
  • Marec N; CytoCell, IRS-UN, Nantes, France.
  • Bossard C; INSERM U1232, IRS-UN, Nantes, France; Pathology Department, CHU Nantes, Nantes, France.
  • Jarry A; INSERM U1232, IRS-UN, Nantes, France.
  • Bridonneau C; Commensal and Probiotic-Host Interactions Laboratory, INRA, Jouy-en-Josas, France.
  • Le Roy A; CRCINA, INSERM, University of Nantes, University of Angers, Nantes, France.
  • Sarrabayrouse G; Vall d'Hebron Institute of Research, Barcelona, Spain.
  • Kerdreux E; CIC, INSERM 1413, CHU Nantes, Hôpital Hôtel-Dieu, Nantes, France; Institut des Maladies de l'Appareil Digestif, CHU Nantes, Hôpital Hôtel-Dieu, Nantes, France.
  • Bourreille A; CIC, INSERM 1413, CHU Nantes, Hôpital Hôtel-Dieu, Nantes, France; Institut des Maladies de l'Appareil Digestif, CHU Nantes, Hôpital Hôtel-Dieu, Nantes, France; INSERM, UMR1235, Nantes, France; Université Nantes, Nantes, France.
  • Sokol H; Commensal and Probiotic-Host Interactions Laboratory, INRA, Jouy-en-Josas, France; Sorbonne University-UPMC Université Paris 06, Ecole Normale Supérieure, CNRS, INSERM, AP-HP, Laboratoires des Biomolécules, Paris, France; Department of Gastroenterology, Saint Antoine Hospital, AP-HP, Paris, France.
  • Jotereau F; CRCINA, INSERM, University of Nantes, University of Angers, Nantes, France. Electronic address: francine.jotereau@univ-nantes.fr.
  • Altare F; CRCINA, INSERM, University of Nantes, University of Angers, Nantes, France. Electronic address: frederic.altare@inserm.fr.
Gastroenterology ; 155(4): 1205-1217, 2018 10.
Article en En | MEDLINE | ID: mdl-29981781
ABSTRACT
BACKGROUND &

AIMS:

Faecalibacterium prausnitzii, a member of the Clostridium IV group of the Firmicutes phylum that is abundant in the intestinal microbiota, has anti-inflammatory effects. The relative level of F prausnitzii is decreased in fecal samples from patients with inflammatory bowel diseases (IBDs) compared with healthy individuals. Reduced F prausnitzii was correlated with relapse of Crohn's disease after surgery. We identified, in human colonic mucosa and blood, a population of T regulatory type 1-like T regulatory (TREG) cells that express CD4 and CD8α (DP8α T cells) and are specific for F prausnitzii. We aimed to determine whether they are altered in patients with IBD.

METHODS:

We isolated DP8α T cells from human colon lamina propria and blood samples and used flow cytometry to detect markers of cells that are of colon origin. We quantified DP8α cells that express colon-specific markers in blood samples from 106 patients with IBD, 12 patients with infectious colitis, and 35 healthy donors (controls). We identified cells that respond to F prausnitzii. Cells were stimulated with anti-CD3, and their production of interleukin 10 was measured by enzyme-linked immunosorbent assay. We compared the frequency and reactivity of cells from patients vs controls using the 2-sided Student t test or 1-way analysis of variance.

RESULTS:

Circulating DP8α T cells that proliferate in response to F prausnitzii express the C-C motif chemokine receptor 6 (CCR6) and C-X-C motif chemokine receptor 6 (CXCR6). These cells also have features of TREG cells, including production of IL-10 and inhibition of T-cell proliferation via CD39 activity. The proportion of circulating CCR6+/CXCR6+ DP8α T cells was significantly reduced (P < .0001) within the total population of CD3+ T cells from patients with IBD compared with patients with infectious colitis or controls. A threshold of <7.875 CCR6+/CXCR6+ DP8α T cells/10,000 CD3+ cells discriminated patients with IBD from those with infectious colitis with 100% specificity and 72.2% sensitivity.

CONCLUSIONS:

We identified a population of gut-derived TREG cells that are reduced in blood samples from patients with IBD compared with patients with infectious colitis or controls. These cells should be studied further to determine the mechanisms of this reduction and how it might contribute to the pathogenesis of IBD and their prognostic or diagnostic value.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Enfermedades Inflamatorias del Intestino / Linfocitos T Reguladores / Colon / Linfocitos T CD8-positivos / Receptores CCR6 / Receptores CXCR6 / Mucosa Intestinal Tipo de estudio: Observational_studies Límite: Humans Idioma: En Revista: Gastroenterology Año: 2018 Tipo del documento: Article País de afiliación: Francia

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Enfermedades Inflamatorias del Intestino / Linfocitos T Reguladores / Colon / Linfocitos T CD8-positivos / Receptores CCR6 / Receptores CXCR6 / Mucosa Intestinal Tipo de estudio: Observational_studies Límite: Humans Idioma: En Revista: Gastroenterology Año: 2018 Tipo del documento: Article País de afiliación: Francia