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

• Published in: JCI insight 2022-06, Vol.7 (12)
• Main Authors: Touch, Sothea, Godefroy, Emmanuelle, Rolhion, Nathalie, Danne, Camille, Oeuvray, Cyriane, Straube, Marjolène, Galbert, Chloé, Brot, Loïc, Alonso Salgueiro, Iria, Chadi, Sead, Ledent, Tatiana, Chatel, Jean-Marc, Langella, Philippe, Jotereau, Francine, Altare, Frédéric, Sokol, Harry
• Format: Article
• Language: English
• Subjects: Gastroenterology
• ISSN: 2379-3708; 2379-3708
• DOI: 10.1172/jci.insight.154722

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.