Microbiota-Dependent Crosstalk Between Macrophages and ILC3 Promotes Intestinal Homeostasis

作者：Arthur Mortha, Aleksey Chudnovskiy, Daigo Hashimoto, Milena Bogunovic, Sean P. Spencer, Yasmine Belkaid, Miriam Mérad · 发表于：Science · 年份：2014 · DOI：10.1126/science.1249288 · 被引用次数：818 · 研究领域：IL-33, ST2, and ILC Pathways、Immune Cell Function and Interaction、Reproductive System and Pregnancy

The intestinal microbiota and tissue-resident myeloid cells promote immune responses that maintain intestinal homeostasis in the host. However, the cellular cues that translate microbial signals into intestinal homeostasis remain unclear. Here, we show that deficient granulocyte-macrophage colony-stimulating factor (GM-CSF) production altered mononuclear phagocyte effector functions and led to reduced regulatory T cell (T(reg)) numbers and impaired oral tolerance. We observed that RORγt(+) innate lymphoid cells (ILCs) are the primary source of GM-CSF in the gut and that ILC-driven GM-CSF production was dependent on the ability of macrophages to sense microbial signals and produce interleukin-1β. Our findings reveal that commensal microbes promote a crosstalk between innate myeloid and lymphoid cells that leads to immune homeostasis in the intestine.