During embryogenesis, the Peyer's patch anlagen are induced by a cell population that produces lymphotoxin (LT) α1β2 following stimulation of IL-7Rα. In this study, we show that the LT-producing cell is localized within the IL-7Rα+ and integrin α4β7 (α4β7)+ population in the embryonic intestine. Lineage commitment to the LT producer phenotype in the fetal liver coincides with expression of α4β7. Before expression of α4β7, the potential of IL-7Rα+ population to generate B cells is lost. However, the progenitors for T cells and LT producer cells reside in the IL-7Rα+α4β7+ cells, but during subsequent differentiation, the potential to give rise to T cells is lost. This IL-7Rα+α4β7 population migrates to the intestine, where it induces the Peyer's patch anlagen. When stimulated with IL-15 or IL-3 and TNF, the intestinal IL-7Rα+α4β7+ population can differentiate into fully competent NK1.1+ NK cells or CD11c+ APCs. Expression of α4β7 is lost during differentiation of both lineages; IL-7Rα expression is lost during NK1.1+ cells differentiation. A newly discovered lineage -IL-7Rα+c-Kit+α 4β7+ population in the fetal liver is committed to T, NK, dendritic, and fetal intestinal LT producer lineage, the latter being an intermediate stage during differentiation of NK and dendritic cells.
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