The formation of lymph nodes (LN) and Peyer's patches (PP) can be distinguished by the requirement of RANK for LN but not IL-7Rα, which is essential for PP development. However, lymphotoxin-αβ (LTαβ) signaling is required for both organs. The cellular basis underlying this dichotomy was revealed by the finding that the fetal IL-7Rα+ population responded equally well to IL-7 and RANKL to express LTαβ. IL-7Rα+ cells harvested from TRAF6−/− embryos expressed LTαβ in response to IL-7 but not RANKL, demonstrating that the RANK-TRAF6 signaling pathway regulates LTαβ expression in LN but not in PP. Soluble IL-7 administered to TRAF6−/− embryos was sufficient to restore LN genesis indicating the functional similarities of the IL-7Rα+ inducer cells for LN and PP genesis.
