Human CD4+CD8α+ Tregs induced by Faecalibacterium prausnitzii protect against intestinal inflammation
Sothea Touch, Emmanuelle Godefroy, Nathalie Rolhion, Camille Danne, Cyriane Oeuvray, Marjolène Straube, Chloé Galbert, Loïc Brot, Iria Alonso Salgueiro, Sead Chadi, Tatiana Ledent, Jean-Marc Chatel, Philippe Langella, Francine Jotereau, Frédéric Altare, Harry Sokol
Sothea Touch, Emmanuelle Godefroy, Nathalie Rolhion, Camille Danne, Cyriane Oeuvray, Marjolène Straube, Chloé Galbert, Loïc Brot, Iria Alonso Salgueiro, Sead Chadi, Tatiana Ledent, Jean-Marc Chatel, Philippe Langella, Francine Jotereau, Frédéric Altare, Harry Sokol
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Research Article Gastroenterology

Human CD4+CD8α+ Tregs induced by Faecalibacterium prausnitzii protect against intestinal inflammation

Abstract

Abundance of Faecalibacterium prausnitzii, a dominant bacterium of the human microbiota that exhibits antiinflammatory effects, is decreased in patients with inflammatory bowel diseases (IBD). In humans, colonic lamina propria contains IL-10–secreting, Foxp3– Tregs characterized by a double expression of CD4 and CD8α (DP8α) and a specificity for F. prausnitzii. This Treg subset is decreased in IBD. The in vivo effect of DP8α cells has not been evaluated yet to our knowledge. Here, using a humanized model of a NSG immunodeficient mouse strain that expresses the HLA D–related allele HLA-DR*0401 but not murine class II (NSG-Ab° DR4) molecules, we demonstrated a protective effect of a HLA-DR*0401–restricted DP8α Treg clone combined with F. prausnitzii administration in a colitis model. In a cohort of patients with IBD, we showed an independent association between the frequency of circulating DP8α cells and disease activity. Finally, we pointed out a positive correlation between F. prausnitzii–specific DP8α Tregs and the amount of F. prausnitzii in fecal microbiota in healthy individuals and patients with ileal Crohn’s disease.

Authors

Sothea Touch, Emmanuelle Godefroy, Nathalie Rolhion, Camille Danne, Cyriane Oeuvray, Marjolène Straube, Chloé Galbert, Loïc Brot, Iria Alonso Salgueiro, Sead Chadi, Tatiana Ledent, Jean-Marc Chatel, Philippe Langella, Francine Jotereau, Frédéric Altare, Harry Sokol

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Figure 4

The frequency of circulating CCR6+CXCR6+ DP8α Tregs and the quantity of F. prausnitzii DNA in fecal microbiota are both decreased in patients with IBD and are positively correlated in patients with Crohn’s disease with ileal involvement.

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The frequency of circulating CCR6+CXCR6+ DP8α Tregs and the quantity of ...
(A) Frequency of circulating CCR6+CXCR6+ DP8α cells per 10,000 CD3+ T cells in the whole cohort of healthy controls (HC, n = 73), patients with Crohn’s disease (CD, n = 185), and patients with ulcerative colitis (UC, n = 65) or (B) according to localization (with or without ileal involvement) in a subcohort of HCs (n = 10) and patients with IBD (n = 10 CD without ileal involvement, n = 28 CD with ileal involvement, and n = 14 patients with UC). (C) Quantity of F. prausnitzii DNA in stool samples in HCs and patients with IBD. (D–F) Spearman’s correlation of the frequency of circulating CCR6+CXCR6+ DP8α cells per 10,000 CD3+ T cells and the quantity of F. prausnitzii DNA in fecal microbiota in the different groups. Results in A–C are represented as the mean ± SEM, For comparison between multiple groups, 1-way ANOVA was performed, and P values of less than 0.05 were considered significant (*P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001). Only significant statistical results after adjustment for false discovery rate are shown (Benjamini-Hochberg, q < 0.1).