Linking the microbiota and metabolic disease with lymphotoxin.

The field of lymphotoxin biology has seen many advances in the past decade. Notably, a role for lymphotoxin as a key effector cytokine has emerged to add to its foundational contribution to lymphoid organogenesis. It is now clear that lymphotoxin contributes to host defense for a wide variety of pathogens, and the lymphotoxin receptor is a defining feature of and regulatory mechanism in both innate and adaptive immunities. Specifically, lymphotoxin contributes to Th education, licensing of IL-22 production from type 3 innate lymphoid cells, and even maintains innate myeloid populations within the fully developed lymph node. Most recently, lymphotoxin has been implicated in regulation of the microbiota and metabolic disease. Early studies revealed that lymphotoxin might influence composition of the commensal microbiota through its regulation of immunological compartmentalization in the gut. Additionally, several epidemiological studies have linked polymorphisms in lymphotoxin to metabolic disease. Studies exploring the role of lymphotoxin in metabolic disease have demonstrated that lymphotoxin may influence metabolism both directly in the liver and indirectly through regulation of gut immune responses. It now appears that lymphotoxin may bridge the gap between altered composition of the commensal microbiota and metabolism.