Innate lymphoid cells are critical regulators of host-microbiota interactions and intestinal homeostasis (P3152)

Abstract

Abstract Mammals are colonized with trillions of commensal bacteria that are essential for normal intestinal physiology and immune cell development. However, dysregulated host-microbiota interactions have been causally linked with the pathogenesis and progression of numerous chronic infectious, inflammatory and metabolic diseases, such as HIV, cancer, obesity, viral hepatitis and inflammatory bowel disease (IBD). Innate lymphoid cells (ILCs) are an emerging family of immune cells that have recently been identified to play critical roles in regulation of immunity, inflammation and homeostasis in the intestine of mice and furthermore alterations in ILC populations have been observed in several chronic human diseases. However, whether ILCs are involved in the regulation of host-microbiota interactions is poorly understood. Here we show that ILCs are critical regulators of host immune responses to the microbiota through several distinct pathways. Surprisingly, abrogation of ILCs or their effector pathways resulted in pathologic host adaptive immune cell responses to resident intestinal microbiota and induction of spontaneous inflammation in the intestine and peripheral tissues. Collectively, these results identify an essential role for ILCs in regulating interactions between the mammalian adaptive immune system and commensal microbiota that dictate the state of intestinal health, and may represent a novel therapeutic target in chronic human disease.