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.
ASJC Scopus subject areas
- Immunology and Allergy