Different cytokines induce surface lymphotoxin-alphabeta on IL-7 receptor-alpha cells that differentially engender lymph nodes and Peyer's patches.

The formation of lymph nodes (LN) and Peyer's patches (PP) can be distinguished by the requirement of RANK for LN but not IL-7R(alpha), which is essential for PP development. However, lymphotoxin-alphabeta (LT(alpha)beta) signaling is required for both organs. The cellular basis underlying this dichotomy was revealed by the finding that the fetal IL-7R(alpha)(+) population responded equally well to IL-7 and RANKL to express LT(alpha)beta. IL-7R(alpha)(+) cells harvested from TRAF6(-/-) embryos expressed LTalphabeta in response to IL-7 but not RANKL, demonstrating that the RANK-TRAF6 signaling pathway regulates LT(alpha)beta 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-7R(alpha)(+) inducer cells for LN and PP genesis.