JCI Insight (Jun 2022)

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

Journal volume & issue
Vol. 7, no. 12

Abstract

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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.

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