Intrinsic lymphotoxin-beta receptor requirement for homeostasis of lymphoid tissue dendritic cells.
The factors regulating dendritic cell (DC) development and homeostasis are incompletely understood. Here, we demonstrate that DCs express the lymphotoxin (LT)-beta receptor (LT beta R) and that in mice lacking the LT beta R in hematopoietic cells, spleen, and lymph node, CD8- DC numbers are reduced. B cells are a key source of LT alpha 1 beta 2 for splenic DC homeostasis, and transgenic overexpression of LT alpha 1 beta 2 on B cells leads to expansion of the CD8- DC compartment. Furthermore, we find that about 5% of splenic DCs are undergoing cell division, and the number of dividing CD8- DCs is disproportionately reduced in the absence of the LT beta R. In parabiosis experiments, splenic DCs were only partially replaced by circulating precursors over a 6 week period. We conclude that LT alpha 1 bet a2 acts on DCs or DC precursors to promote DC homeostasis, and we suggest that DC proliferation is an important pathway for locally maintaining these cells in the steady state.
Kabashima
Kenji
K
Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, California 94143, USA.
Banks
Theresa A
TA
Ansel
K Mark
KM
Lu
Theresa T
TT
Ware
Carl F
CF
Cyster
Jason G
JG
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D001483:Base Sequence; D016827:CD8 Antigens / Q000378:metabolism; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000166:cytology / Q000502:physiology*; D006706:Homeostasis; D008221:Lymphoid Tissue / Q000166:cytology*; D053259:Lymphotoxin beta Receptor; D051379:Mice; D008969:Molecular Sequence Data; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D015854:Up-Regulation
D016827:CD8 Antigens; C505699:Ltbr protein, mouse; D053259:Lymphotoxin beta Receptor; D018124:Receptors, Tumor Necrosis Factor