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

• DOI: 10.1172/jci.insight.154722
• Publication Date: 2022-05-10T16:01:16Z
• Authors: Sothea Touch; Emmanuelle Godefroy; Nathalie Rolhion; Camille Danne; Cyriane Oeuvray; Marjolène Straube; Chloé Galbert; Loïc Brot; Iria Alonso Salgu...; Sead Chadi; Tatiana Ledent; Jean-Marc Chatel; Philippe Langella; Francine Jotereau; Frédéric Altare; Harry Sokol
• Keywords: Inflammation; 0303 health sciences; Faecalibacterium prausnitzii; Gastroenterology; R; Colitis; Inflammatory Bowel Diseases; T-Lymphocytes, Regulatory; 3. Good health; Mice; 03 medical and health sciences; Medicine; Animals; Humans

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.