Human CD4+/CD8α+ regulatory T cells induced by Faecalibacterium prausnitzii protect against intestinal inflammation

Faecalibacterium prausnitzii (F. prausnitzii), a dominant bacterium of the human microbiota, is decreased in patients with inflammatory bowel diseases (IBD) and exhibits anti-inflammatory effects. In human, colonic lamina propria contains IL-10-positive, Foxp3-negative regulatory T cells (Treg) characterized by a double expression of CD4 and CD8alpha (DP8alpha) and a specificity for F. prausnitzii. This Treg subset is decreased in IBD. The in vivo effect of DP8alpha cells has not been evaluated yet. Here, using a humanized model of NSG immunodeficient mouse strain that expresses human leucocyte antigen D-related 4 (HLA-DR4) but not murine class II (NSG-Ab DR4), we demonstrated a protective effect of DP8alpha Tregs 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 DP8alpha cells and disease activity. Finally, we pointed out a positive correlation between F. prausnitzii-specific DP8alpha; Tregs and the amount of F. prausnitzii in fecal microbiota in healthy individuals and patients with ileal Crohn s disease. ### Competing Interest Statement HS received unrestricted study grants from Danone, Biocodex, and Enterome; board membership, consultancy, or lecture fees from Carenity, Abbvie, Astellas, Danone, Ferring, Mayoly Spindler, MSD, Novartis, Roche, Tillots, Enterome, Maat, BiomX, Biose, Novartis, and Takeda; and a co-founder of Exeliom bioscience. Other authors have declared that no conflict of interest exists.