Human CD4+CD8α+ Tregs induced by Faecalibacterium prausnitzii protect against intestinal inflammation
Sothea Touch, … , Frédéric Altare, Harry Sokol
Sothea Touch, … , Frédéric Altare, Harry Sokol
Published May 10, 2022
Citation Information: JCI Insight. 2022;7(12):e154722. https://doi.org/10.1172/jci.insight.154722.
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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 2

Administration of DP8α Tregs and F. prausnitzii, but not that of DP8α or F. prausnitzii alone, protects NSG-Ab°DR4 mice from DSS-induced colitis.

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Administration of DP8α Tregs and F. prausnitzii, but not that of DP8α or...
(A) Experimental outline: NSG-Ab°DR4 female mice were injected i.p. with PBS or human peripheral CD4 effector T cells with either a human DRb1*0401-restricted DP8α Treg clone or PBS and received daily gavage with 1 × 108 CFU of F. prausnitzii or 200 μL vehicle 1X PBS for 10 days before 1% DSS supplementation in drinking water for 7 days, followed by 4 days of regular drinking water. (B) Body weight and (C) disease activity index (DAI) were evaluated in the CD4+PBS (n = 44), CD4+DP8α (n = 20), and CD4+DP8α+F. prausnitzii (n = 45) groups in 5 independent experiments. (D and E) Histological score was assessed in the CD4+PBS (n = 30), CD4+DP8α (n = 9), and CD4+DP8α+F. prausnitzii (n = 29) groups in 3 independent experiments. (F) Body weight and (G) DAI were also evaluated in the CD4+PBS group (n = 10, open circles), as compared with the CD4+F. prausnitzii group (n = 11, purple circles) in another series of 2 independent experiments. Body weight and DAI are presented 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 < 0.0001, §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). The symbol † indicates the beginning of mortality.