Reciprocal Regulation of Lymphoid Tissue Development in the Large Intestine by IL-25 and IL-23: Regulation of colonic ILF by IL-25/IL-23

Isolated lymphoid follicles (ILF) develop post-birth in the small and large intestines (SI and LI) and represent a dynamic response of the gut immune system to the microbiota. Despite their similarities, ILF development in the SI and LI differs on a number of levels. We show that unlike ILF in the SI, the microbiota inhibits ILF development as conventionalisation of germ-free mice reduced colonic ILF. From this, we identified a novel mechanism regulating colonic ILF development through the action of IL-25 on IL-23 and its ability to modulate Treg differentiation. Colonic ILF develop in the absence of a number of factors required for 30 the development of their SI counterparts and can be specifically suppressed by factors other than IL-25. However, IL-23 is the only factor identified that specifically promotes colonic ILF without affecting SI-ILF development. Both IL-23 and ILF are associated with inflammatory bowel disease, suggesting that disruption to this pathway may have an important role in the breakdown of microbiota-immune homeostasis.