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PMID: 10477548 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The requirement of membrane lymphotoxin for the presence of dendritic cells in lymphoid tissues.

The Journal of experimental medicine ·Vol. 190 ·No. 5 ·1999-09-06 ·Pages 629-38

Wu Q, Wang Y, Wang J, Hedgeman EO, Browning JL, Fu YX

Abstract

Although several cytokines, including tumor necrosis factor (TNF), can promote the growth of dendritic cells (DCs) in vitro, the cytokines that naturally regulate DC development and function in vivo have not been well defined. Here, we report that membrane lymphotoxin (LT), instead of TNF, regulates the migration of DCs in the spleen. LTalpha(-/-) mice, lacking membrane LTalpha/beta and LTalpha(3), show markedly reduced numbers of DCs in the spleen. Unlike wild-type mice and TNF(-/-) mice that have densely clustered DCs in the T cell zone and around the marginal zone, splenic DCs in LTalpha(-/-) mice are randomly distributed. The reduced number of DCs in lymphoid tissues of LTalpha(-/-) mice is associated with an increased number of DCs in nonlymphoid tissues. The number of splenic DCs in LTalpha(-/-) mice is restored when additional LT-expressing cells are provided. Blocking membrane LTalpha/beta in wild-type mice markedly diminishes the accumulation of DCs in lymphoid tissues. These data suggest that membrane LT is an essential ligand for the presence of DCs in the spleen. Mice deficient in TNF receptor, which is the receptor for both soluble LTalpha(3) and TNF-alpha(3) trimers, have normal numbers of DCs. However, LTbetaR(-/-) mice show reduced numbers of DCs, similar to the mice lacking membrane LT alpha/beta. Taken together, these results support the notion that the signaling via LTbetaR by membrane LTalpha/beta is required for the presence of DCs in lymphoid tissues.

MeSH Terms
Animals Bone Marrow Cells/immunology Cell Count Cell Movement/immunology,physiology Dendritic Cells/immunology,physiology Female Lymphocyte Culture Test, Mixed Lymphoid Tissue/cytology,immunology Lymphotoxin beta Receptor Lymphotoxin-alpha/genetics,physiology Male Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Phenotype Receptors, Tumor Necrosis Factor/deficiency,genetics,physiology Signal Transduction Solubility Spleen/cytology,immunology Tumor Necrosis Factor-alpha/deficiency,genetics,physiology
Chemicals
Ltbr protein, mouse Lymphotoxin beta Receptor Lymphotoxin-alpha Receptors, Tumor Necrosis Factor Tumor Necrosis Factor-alpha
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Wu Q
Department of Pathology, The University of Chicago, Chicago, Illinois 60637, USA.
Wang Y
Wang J
Hedgeman E O
Browning J L
Fu Y X
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.190.5.629
Published
1999-09-06
Pages
629-38
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2195624
Subset
IM
Grants
NIAID NIH HHS · AI01431 · United States
NICHD NIH HHS · HD37104 · United States
NICHD NIH HHS · HD37600 · United States
External Links
PubMed source DOI: 10.1084/jem.190.5.629 PMC Full Text View journal details
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