The Peter Gorer Department of Immunobiology, King's College London, London, UK.
The Francis Crick Institute, London, UK.
EMBO J. 2018 Mar 1;37(5). doi: 10.15252/embj.201797537. Epub 2018 Jan 29.
Intestinal homeostasis relies on a continuous dialogue between the commensal bacteria and the immune system. Natural killer T (NKT) cells, which recognize CD1d-restricted microbial lipids and self-lipids, contribute to the regulation of mucosal immunity, yet the mechanisms underlying their functions remain poorly understood. Here, we demonstrate that NKT cells respond to intestinal lipids and CD11c cells (including dendritic cells (DCs) and macrophages) are essential to mediate lipid presentation within the gut ultimately controlling intestinal NKT cell homeostasis and activation. Conversely, CD1d and NKT cells participate in the control of the intestinal bacteria composition and compartmentalization, in the regulation of the IgA repertoire and in the induction of regulatory T cells within the gut. These changes in intestinal homeostasis require CD1d expression on DC/macrophage populations as mice with conditional deletion of CD1d on CD11c cells exhibit dysbiosis and altered immune homeostasis. These results unveil the importance of CD11c cells in controlling lipid-dependent immunity in the intestinal compartment and reveal an NKT cell-DC crosstalk as a key mechanism for the regulation of gut homeostasis.
肠道内稳态依赖于共生菌与免疫系统之间的持续对话。自然杀伤 T (NKT) 细胞识别 CD1d 限制的微生物脂质和自身脂质，有助于调节黏膜免疫，但它们的功能机制仍知之甚少。在这里，我们证明 NKT 细胞对肠道内脂质有反应，而 CD11c 细胞（包括树突状细胞 (DC) 和巨噬细胞）对于在肠道内介导脂质呈递至关重要，从而最终控制肠道 NKT 细胞内稳态和激活。相反，CD1d 和 NKT 细胞参与控制肠道细菌组成和区室化、调节 IgA 库以及诱导肠道内调节性 T 细胞。这些肠道内稳态的变化需要 DC/巨噬细胞群上的 CD1d 表达，因为条件性敲除 CD11c 细胞上的 CD1d 的小鼠表现出菌群失调和免疫内稳态改变。这些结果揭示了 CD11c 细胞在控制肠道内脂质依赖性免疫中的重要性，并揭示了 NKT 细胞-DC 细胞串扰作为调节肠道内稳态的关键机制。
