Signal via lymphotoxin-beta R on bone marrow stromal cells is required for an early checkpoint of NK cell development.
NK cells play an important role in the immune system but the cellular and molecular requirements for their early development are poorly understood. Lymphotoxin-alpha (LTalpha)(-/-) and LTbetaR(-/-) mice show a severe systemic reduction of NK cells, which provides an excellent model to study NK cell development. In this study, we show that the bone marrow (BM) or fetal liver cells from LTalpha(-/-) or LTbetaR(-/-) mice efficiently develop into mature NK cells in the presence of stromal cells from wild-type mice but not from LTalpha(-/-) or LTbetaR(-/-) mice. Direct activation of LTbetaR-expressing BM stromal cells is shown to promote to early NK cell development in vitro. Furthermore, the blockade of the interaction between LT and LTbetaR in adult wild-type mice by administration of LTbetaR-Ig impairs the development of NK cells in vivo. Together, these results indicate that the signal via LTbetaR on BM stromal cells by membrane LT is an important pathway for early NK cell development.
Wu
Q
Q
Department of Pathology and Neurology, University of Chicago, Chicago, IL 60637, USA.
Sun
Y
Y
Wang
J
J
Lin
X
X
Wang
Y
Y
Pegg
L E
LE
Fütterer
A
A
Pfeffer
K
K
Fu
Y X
YX
D019264:Adoptive Transfer; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology* / Q000473:pathology; D006706:Homeostasis / Q000276:immunology; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics; D018655:Lymphocyte Count; D008221:Lymphoid Tissue / Q000276:immunology / Q000473:pathology; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology / Q000628:therapy; D053259:Lymphotoxin beta Receptor; D008233:Lymphotoxin-alpha / Q000235:genetics / Q000378:metabolism*; D053308:Lymphotoxin-beta; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018124:Receptors, Tumor Necrosis Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D017154:Stromal Cells / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000473:pathology
C505887:Ltb protein, mouse; C505699:Ltbr protein, mouse; D053259:Lymphotoxin beta Receptor; D008233:Lymphotoxin-alpha; D053308:Lymphotoxin-beta; D008565:Membrane Proteins; D018124:Receptors, Tumor Necrosis Factor