Expression of α₄β₇ integrin defines a distinct pathway of lymphoid progenitors committed to T cells, fetal intestinal lymphotoxin producer, NK, and dendritic cells

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.