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

Emmanuelle Godefroy; Joudy Alameddine; Emmanuel Montassier; Justine Mathé; Juliette Desfrançois-Noël; Nadège Marec; Céline Bossard; Anne Jarry; Chantal Bridonneau; Amandine Le Roy; Guillaume Sarrabayrouse; Elise Kerdreux; Arnaud Bourreille; Harry Sokol; Francine Jotereau; Frédéric Altare

doi:10.1053/j.gastro.2018.06.078

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

Emmanuelle Godefroy ¹ Joudy Alameddine ¹ Emmanuel Montassier ^{2, 3} Justine Mathé ¹ Juliette Desfrançois-Noël ⁴ Nadège Marec ⁴ Céline Bossard ^{5, 6} Anne Jarry ⁵ Chantal Bridonneau ⁷ Amandine Le Roy ¹ Guillaume Sarrabayrouse ⁸ Elise Kerdreux ^{9, 10} Arnaud Bourreille ^{9, 10, 11} Harry Sokol ^{7, 12, 13} Francine Jotereau ¹ Frédéric Altare ^{1, *}

* Corresponding author

1 CRCINA - Département INCIT - Equipe 5 - Host-pathogen interactions in the regulation of immune responses

CRCINA - Centre de recherche de Cancérologie et d'Immunologie / Nantes - Angers

2 Service des Urgences [CHU Nantes]

3 MiHAR - Microbiotes, Hôtes, Antibiotiques et Résistances bactériennes (MiHAR)

4 CRCINA – Unité Inserm U1232 - Plate-forme CytoCell [Nantes]

CRCINA - Centre de recherche de Cancérologie et d'Immunologie / Nantes - Angers

5 CRCINA - Département INCIT - Equipe 3 - Anti-tumor immunosurveillances and immunotherapy

CRCINA - Centre de recherche de Cancérologie et d'Immunologie / Nantes - Angers

6 Département de Pathologie [CHU Nantes]

7 Commensal and probiotics-host interactions laboratory [INRA, Jouy-en-Josas]

8 Vall d’Hebron Institute of Research [Barcelona, Spain]

9 CIC Nantes - Centre d’Investigation Clinique de Nantes

10 Institut des Maladies de l'Appareil Digestif

11 TENS - The Enteric Nervous System in gut and brain disorders [U1235]

12 LBM UMR 7203 - Laboratoire des biomolécules

13 Département de Gastroentérologie [AP-HP Hôpital Saint-Antoine]

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.

Keywords : Bacteria Immune Regulation Microbiota T-Cell Response

Document type :

Journal articles

Domain :

Life Sciences [q-bio] / Immunology

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https://www.hal.inserm.fr/inserm-01968888
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Submitted on : Thursday, January 3, 2019 - 2:22:25 PM
Last modification on : Wednesday, February 19, 2020 - 2:50:50 PM

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

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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

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