Sorbonne University, INSERM, Saint-Antoine Center of Research, Centre De Recherche scientifique Saint-Antoine, Assistance Publique - Hôpitaux de Paris (AP-HP), Saint Antoine Hospital, Gastroenterology Department, Paris, France.
Paris Center for Microbiome Medicine, University Hospital Federations, Paris, France.
JCI Insight. 2022 Jun 22;7(12):e154722. 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-DR0401 but not murine class II (NSG-Ab° DR4) molecules, we demonstrated a protective effect of a HLA-DR0401-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.
丰度帕劳斯氏菌（Faecalibacterium prausnitzii），一种具有抗炎作用的人类微生物群主要细菌，在炎症性肠病（IBD）患者中减少。在人类中，结肠固有层含有分泌白细胞介素 10（IL-10）的、Foxp3+ Tregs，其特征为双重表达 CD4 和 CD8α（DP8α），并对 F. prausnitzii 具有特异性。在 IBD 中，这种 Treg 亚群减少。据我们所知，DP8α 细胞的体内作用尚未得到评估。在这里，我们使用一种表达 HLA D 相关等位基因 HLA-DR0401 但不表达鼠类 II 类（NSG-Ab° DR4）分子的 NSG 免疫缺陷小鼠品系的人源化模型，证明了 HLA-DR0401 限制性 DP8α Treg 克隆与 F. prausnitzii 联合给药在结肠炎模型中的保护作用。在一组 IBD 患者中，我们显示循环 DP8α 细胞的频率与疾病活动度之间存在独立关联。最后，我们指出在健康个体和回肠克罗恩病患者的粪便微生物群中，F. prausnitzii 特异性 DP8α Tregs 与 F. prausnitzii 的数量之间存在正相关。
