Expression of alpha(4)beta(7) 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) alpha(1)beta(2) following stimulation of IL-7Ralpha. In this study, we show that the LT-producing cell is localized within the IL-7Ralpha(+) and integrin alpha(4)beta(7) (alpha(4)beta(7))(+) population in the embryonic intestine. Lineage commitment to the LT producer phenotype in the fetal liver coincides with expression of alpha(4)beta(7). Before expression of alpha(4)beta(7), the potential of IL-7Ralpha(+) population to generate B cells is lost. However, the progenitors for T cells and LT producer cells reside in the IL-7Ralpha(+)alpha(4)beta(7)(+) cells, but during subsequent differentiation, the potential to give rise to T cells is lost. This IL-7Ralpha(+)alpha(4)beta(7)(+) 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-7Ralpha(+)alpha(4)beta(7)(+) population can differentiate into fully competent NK1.1(+) NK cells or CD11c(+) APCs. Expression of alpha(4)beta(7) is lost during differentiation of both lineages; IL-7Ralpha expression is lost during NK1.1(+) cells differentiation. A newly discovered lineage(-)IL-7Ralpha(+)c-Kit(+)alpha(4)beta(7)(+) 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.
Yoshida
H
H
Department of Molecular Genetics, Graduate School of Medicine, and Department of Immunology, Institute for Frontier Medical Sciences, Kyoto University, Sakyo, Kyoto, Japan. hyoshida@virus.kyoto-u.ac.jp
Kawamoto
H
H
Santee
S M
SM
Hashi
H
H
Honda
K
K
Nishikawa
S
S
Ware
C F
CF
Katsura
Y
Y
Nishikawa
S I
SI
D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D005260:Female; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D019409:Interleukin-15 / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology; D008233:Lymphotoxin-alpha / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D010581:Peyer's Patches / Q000166:cytology / Q000196:embryology* / Q000276:immunology*; D011247:Pregnancy; D020395:Receptors, Interleukin-7 / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology* / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
D016023:Integrins; D019409:Interleukin-15; D007377:Interleukin-3; D008233:Lymphotoxin-alpha; D020395:Receptors, Interleukin-7; C071777:integrin alpha4beta7; C415350:interleukin-7 receptor, alpha chain