School of Immunology and Microbial Sciences, King's College London, London, UK.
École Normale Supérieure de Lyon, Claude Bernard Lyon 1 University, Lyon, France.
Nat Commun. 2024 May 14;15(1):4051. doi: 10.1038/s41467-024-48267-4.
Intestinal homeostasis is maintained by the response of gut-associated lymphoid tissue to bacteria transported across the follicle associated epithelium into the subepithelial dome. The initial response to antigens and how bacteria are handled is incompletely understood. By iterative application of spatial transcriptomics and multiplexed single-cell technologies, we identify that the double negative 2 subset of B cells, previously associated with autoimmune diseases, is present in the subepithelial dome in health. We show that in this location double negative 2 B cells interact with dendritic cells co-expressing the lupus autoantigens DNASE1L3 and C1q and microbicides. We observe that in humans, but not in mice, dendritic cells expressing DNASE1L3 are associated with sampled bacteria but not DNA derived from apoptotic cells. We propose that fundamental features of autoimmune diseases are microbiota-associated, interacting components of normal intestinal immunity.
肠道内环境的稳定依赖于肠相关淋巴组织对穿过滤泡相关上皮进入黏膜下穹窿的细菌的反应。对于抗原的初始反应以及细菌的处理方式尚未完全清楚。通过空间转录组学和多重单细胞技术的反复应用，我们发现先前与自身免疫性疾病相关的双阴性 2 型 B 细胞亚群存在于健康状态下的黏膜下穹窿中。我们表明，在这个位置，双阴性 2 型 B 细胞与共表达狼疮自身抗原 DNASE1L3 和 C1q 以及微生物杀伤剂的树突状细胞相互作用。我们观察到，在人类中，但不在小鼠中，表达 DNASE1L3 的树突状细胞与采样细菌而非源自凋亡细胞的 DNA 相关。我们提出，自身免疫性疾病的基本特征是与微生物组相关的、正常肠道免疫的相互作用成分。
