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 1

Detection of human cells in whole blood and the colon lamina propria of NSG-Ab°DR4 mice.

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Detection of human cells in whole blood and the colon lamina propria of ...
(A) The presence of human cells after injection of CD4+ effector T cells in presence or absence of DP8α Tregs was assessed by flow cytometry in 2 independent experiments in the peripheral blood 10 days after injection, before the start of DSS treatment (day 0) and in the colon lamina propria 8 days after the start of DSS treatment (day 8). (B) After doublet discrimination and exclusion of debris, human CD3+ and human CD4+ cells were analyzed among human CD45+ (hCD45+) and murine CD45– (mCD45–) cells. (C) Frequency of human CD45+ and mouse CD45– cells among total CD45+ cells in CD4+PBS (n = 5, empty dots) and CD4+DP8α (n = 5, black dots) groups. (D) Detection of human cells in the colon lamina propria was determined by the expression of human CD3 and the absence of expression of mouse CD45 among total mCD45+ and human CD3+ cells. (E) Frequency of human CD3+ and mouse CD45– cells among total colonic mouse CD45+ and human CD3+ cells in CD4+PBS (n = 5, empty dots) and CD4+DP8α (n = 4, black dots) groups. Original magnification, ×4. (F and G) DP8α clone was injected i.p. and analyzed by flow cytometry in the colon lamina propria of the mice after 10 days of daily gavage with F. prausnitzii followed by 0, 4, 7, 9, or 11 days of treatment with DSS. “Non-injected” indicates the control group without cells injected. Results are presented as the mean ± SEM.