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 3

Administration of DP8α Tregs and F. prausnitzii lowers inflammation induced by DSS-induced colitis in NSG-Ab°DR4 mice.

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Administration of DP8α Tregs and F. prausnitzii lowers inflammation indu...
(A) Experimental outline: NSG-Ab°DR4 female mice were injected i.p. with 2 × 106 human peripheral CD4 effector T cells alone or in combination with 2 × 106 human DRb1*0401-restricted DP8α clones and received daily gavage with 200 μL 1X PBS or 1 × 108 CFU of F. prausnitzii, respectively, for 10 days before 1% DSS supplementation in drinking water for 7 days. Mice were sacrificed at day 7. (B) Body weight and (C) disease activity index were assessed during the protocol in all groups of mice. (D and E) mRNA levels of Reg3b and Reg3g were analyzed by RT-qPCR in the proximal colon at day 7. (F) Lipocalin-2 secretion (pg/g of colon content) was measured by ELISA in the colon content at day 7. (G and H) Histological score was obtained from the colons of mice at day 7. Original magnification, ×10. Results 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 < 0.0001). Only significant statistical results after adjustment for false discovery rate are shown (Benjamini-Hochberg, q < 0.1). Each figure is representative of n = 3 independent experiments (CD4+PBS, n = 17; CD4+DP8α, n = 16; CD4+DP8α+F. prausnitzii, n = 17).